BACKGROUND Prostate cancer(PCa)is a widespread malignancy,predominantly affecting elderly males,and current methods for diagnosis and treatment of this disease continue to fall short.The marker Ki-67(MKI67)has been pr...BACKGROUND Prostate cancer(PCa)is a widespread malignancy,predominantly affecting elderly males,and current methods for diagnosis and treatment of this disease continue to fall short.The marker Ki-67(MKI67)has been previously demonstrated to correlate with the proliferation and metastasis of various cancer cells,including those of PCa.Hence,verifying the association between MKI67 and the diagnosis and prognosis of PCa,using bioinformatics databases and clinical data analysis,carries significant clinical implications.AIM To explore the diagnostic and prognostic efficacy of antigens identified by MKI67 expression in PCa.METHODS For cohort 1,the efficacy of MKI67 diagnosis was evaluated using data from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases.For cohort 2,the diagnostic and prognostic power of MKI67 expression was further validated using data from 271 patients with clinical PCa.RESULTS In cohort 1,MKI67 expression was correlated with prostate-specific antigen(PSA),Gleason Score,T stage,and N stage.The receiver operating characteristic(ROC)curve showed a strong diagnostic ability,and the Kaplan-Meier method demonstrated that MKI67 expression was negatively associated with the progression-free interval(PFI).The time-ROC curve displayed a weak prognostic capability for MKI67 expression in PCa.In cohort 2,MKI67 expression was significantly related to the Gleason Score,T stage,and N stage;however,it was negatively associated with the PFI.The time-ROC curve revealed the stronger prognostic capability of MKI67 in patients with PCa.Multivariate COX regression analysis was performed to select risk factors,including PSA level,N stage,and MKI67 expression.A nomogram was established to predict the 3-year PFI.CONCLUSION MKI67 expression was positively associated with the Gleason Score,T stage,and N stage and showed a strong diagnostic and prognostic ability in PCa.展开更多
BACKGROUND Ferroptosis has recently been associated with multiple degenerative diseases.Ferroptosis induction in cancer cells is a feasible method for treating neoplastic diseases.However,the association of iron proli...BACKGROUND Ferroptosis has recently been associated with multiple degenerative diseases.Ferroptosis induction in cancer cells is a feasible method for treating neoplastic diseases.However,the association of iron proliferation-related genes with prognosis in HER2+breast cancer(BC)patients is unclear.AIM To identify and evaluate fresh ferroptosis-related biomarkers for HER2+BC.METHODS First,we obtained the mRNA expression profiles and clinical information of HER2+BC patients from the TCGA and METABRIC public databases.A four gene prediction model comprising PROM2,SLC7A11,FANCD2,and FH was subsequently developed in the TCGA cohort and confirmed in the METABRIC cohort.Patients were stratified into high-risk and low-risk groups based on their median risk score,an independent predictor of overall survival(OS).Based on these findings,immune infiltration,mutations,and medication sensitivity were analyzed in various risk groupings.Additionally,we assessed patient prognosis by combining the tumor mutation burden(TMB)with risk score.Finally,we evaluated the expression of critical genes by analyzing single-cell RNA sequencing(scRNA-seq)data from malignant vs normal epithelial cells.RESULTS We found that the higher the risk score was,the worse the prognosis was(P<0.05).We also found that the immune cell infiltration,mutation,and drug sensitivity were different between the different risk groups.The highrisk subgroup was associated with lower immune scores and high TMB.Moreover,we found that the combination of the TMB and risk score could stratify patients into three groups with distinct prognoses.HRisk-HTMB patients had the worst prognosis,whereas LRisk-LTMB patients had the best prognosis(P<0.0001).Analysis of the scRNAseq data showed that PROM2,SLC7A11,and FANCD2 were significantly differentially expressed,whereas FH was not,suggesting that these genes are expressed mainly in cancer epithelial cells(P<0.01).CONCLUSION Our model helps guide the prognosis of HER2+breast cancer patients,and its combination with the TMB can aid in more accurate assessment of patient prognosis and provide new ideas for further diagnosis and treatment.展开更多
BACKGROUND Eosinophilic gastroenteritis(EGE)is a chronic recurrent disease with abnormal eosinophilic infiltration in the gastrointestinal tract.Glucocorticoids remain the most common treatment method.However,disease ...BACKGROUND Eosinophilic gastroenteritis(EGE)is a chronic recurrent disease with abnormal eosinophilic infiltration in the gastrointestinal tract.Glucocorticoids remain the most common treatment method.However,disease relapse and glucocorticoid dependence remain notable problems.To date,few studies have illuminated the prognosis of EGE and risk factors for disease relapse.AIM To describe the clinical characteristics of EGE and possible predictive factors for disease relapse based on long-term follow-up.METHODS This was a retrospective cohort study of 55 patients diagnosed with EGE admitted to one medical center between 2013 and 2022.Clinical records were collected and analyzed.Kaplan-Meier curves and log-rank tests were conducted to reveal the risk factors for long-term relapse-free survival(RFS).RESULTS EGE showed a median onset age of 38 years and a slight female predominance(56.4%).The main clinical symptoms were abdominal pain(89.1%),diarrhea(61.8%),nausea(52.7%),distension(49.1%)and vomiting(47.3%).Forty-three(78.2%)patients received glucocorticoid treatment,and compared with patients without glucocorticoid treatments,they were more likely to have elevated serum immunoglobin E(IgE)(86.8%vs 50.0%,P=0.022)and descending duodenal involvement(62.8%vs 27.3%,P=0.046)at diagnosis.With a median follow-up of 67 mo,all patients survived,and 56.4%had at least one relapse.Six variables at baseline might have been associated with the overall RFS rate,including age at diagnosis<40 years[hazard ratio(HR)2.0408,95%confidence interval(CI):1.0082–4.1312,P=0.044],body mass index(BMI)>24 kg/m^(2)(HR 0.3922,95%CI:0.1916-0.8027,P=0.014),disease duration from symptom onset to diagnosis>3.5 mo(HR 2.4725,95%CI:1.220-5.0110,P=0.011),vomiting(HR 3.1259,95%CI:1.5246-6.4093,P=0.001),total serum IgE>300 KU/L at diagnosis(HR 0.2773,95%CI:0.1204-0.6384,P=0.022)and glucocorticoid treatment(HR 6.1434,95%CI:2.8446-13.2676,P=0.003).CONCLUSION In patients with EGE,younger onset age,longer disease course,vomiting and glucocorticoid treatment were risk factors for disease relapse,whereas higher BMI and total IgE level at baseline were protective.展开更多
Primary tumors of the central nervous system(CNS)are classified into over 100 different histological types.The most common type of glioma is derived from astrocytes,and the most invasive glioblastoma(WHO IV)accounts f...Primary tumors of the central nervous system(CNS)are classified into over 100 different histological types.The most common type of glioma is derived from astrocytes,and the most invasive glioblastoma(WHO IV)accounts for over 57%of these tumors.Glioblastoma(GBM)is the most common and fatal tumor of the CNS,with strong growth and invasion capabilities,which makes complete surgical resection almost impossible.Despite various treatment methods such as surgery,radiotherapy,and chemotherapy,glioma is still an incurable disease,and the median survival time of patients with GBM is shorter than 15 months.Thus,molecular mechanisms of GBM characteristic invasive growth need to be clarified to improve the poor prognosis.Glutamate ionotropic receptor kainate type subunit 1(GRIK1)is essential for brain function and is involved in many mental and neurological diseases.However,GRIK1’s pathogenic roles and mechanisms in GBM are still unknown.Single-nuclear RNA sequencing of primary and recurrent GBM samples revealed that GRIK1 expression was noticeably higher in the recurrent samples.Moreover,immunohistochemical staining of an array of GBM samples showed that high levels of GRIK1 correlated with poor prognosis of GBM,consistent with The Cancer Genome Atlas database.Knockdown of GRIK1 retarded GBM cells growth,migration,and invasion.Taken together,these findings show that GRIK1 is a unique and important component in the development of GBM and may be considered as a biomarker for the diagnosis and therapy in individuals with GBM.展开更多
BACKGROUND Lactate,previously considered a metabolic byproduct,is pivotal in cancer progression and maintaining the immunosuppressive tumor microenvironment.Further investigations confirmed that lactate is a primary r...BACKGROUND Lactate,previously considered a metabolic byproduct,is pivotal in cancer progression and maintaining the immunosuppressive tumor microenvironment.Further investigations confirmed that lactate is a primary regulator,introducing recently described post-translational modifications of histone and non-histone proteins,termed lysine lactylation.Pancreatic adenocarcinomas are characterized by increased glycolysis and lactate accumulation.However,our understanding of lactylation-related genes in pancreatic adenocarcinomas remains limited.AIM To construct a novel lactylation-related gene signature to predict the survival of patients with pancreatic cancer.METHODS RNA-seq and clinical data of pancreatic adenocarcinoma(PDAC)were obtained from the GTEx(Genotype-Tissue Expression)and TCGA(The Cancer Genome Atlas)databases via Xena Explorer,and GSE62452 datasets from GEO.Data on lactylation-related genes were obtained from publicly available sources.Differential expressed genes(DEGs)were acquired by using R package“DESeq2”in R.Univariate COX regression analysis,LASSO Cox and multivariate Cox regressions were produced to construct the lactylation-related prognostic model.Further analyses,including functional enrichment,ESTIMATE,and CIBERSORT,were performed to analyze immune status and treatment responses in patients with pancreatic cancer.PDAC and normal human cell lines were subjected to western blot analysis under lactic acid intervention;two PDAC cell lines with the most pronounced lactylation were selected.Subsequently,RT-PCR was employed to assess the expression of LRGs genes;SLC16A1,which showed the highest expression,was selected for further investigation.SLC16A1-mediated lactylation was analyzed by immunofluorescence,lactate production analysis,colony formation,transwell,and wound healing assays to investigate its role in promoting the proliferation and migration of PDAC cells.In vivo validation was performed using an established tumor model.RESULTS In this study,we successfully identified 10 differentially expressed lactylation-related genes(LRGs)with prognostic value.Subsequently,a lactylation-related signature was developed based on five OS-related lactylationrelated genes(SLC16A1,HLA-DRB1,KCNN4,KIF23,and HPDL)using Lasso Cox hazard regression analysis.Subsequently,we evaluated the clinical significance of the lactylation-related genes in pancreatic adenocarcinoma.A comprehensive examination of infiltrating immune cells and tumor mutation burden was conducted across different subgroups.Furthermore,we demonstrated that SLC16A1 modulates lactylation in pancreatic cancer cells through lactate transport.Both in vivo and in vitro experiments showed that decreasing SLC16A1 Level and its lactylation significantly inhibited tumor progression,indicating the potential of targeting the SLC16A1/Lactylation-associated signaling pathway as a therapeutic strategy against pancreatic adenocarcinoma.CONCLUSION We constructed a novel lactylation-related prognostic signature to predict OS,immune status,and treatment response of patients with pancreatic adenocarcinoma,providing new strategic directions and antitumor immunotherapies.展开更多
BACKGROUND:We aimed to observe the dynamic changes in glucose metabolic reprogrammingrelated parameters and their ability to predict neurological prognosis and all-cause mortality in cardiac arrest patients after the ...BACKGROUND:We aimed to observe the dynamic changes in glucose metabolic reprogrammingrelated parameters and their ability to predict neurological prognosis and all-cause mortality in cardiac arrest patients after the restoration of spontaneous circulation(ROSC).METHODS:Adult cardiac arrest patients after ROSC who were admitted to the emergency or cardiac intensive care unit of the First Aflliated Hospital of Dalian Medical University from August 1,2017,to May 30,2021,were enrolled.According to 28-day survival,the patients were divided into a non-survival group(n=82) and a survival group(n=38).Healthy adult volunteers(n=40) of similar ages and sexes were selected as controls.The serum levels of glucose metabolic reprogrammingrelated parameters(lactate dehydrogenase [LDH],lactate and pyruvate),neuron-specific enolase(NSE) and interleukin 6(IL-6) were measured on days 1,3,and 7 after ROSC.The Acute Physiology and Chronic Health Evaluation II(APACHE II) score and Sequential Organ Failure Assessment(SOFA) score were calculated.The Cerebral Performance Category(CPC) score was recorded on day 28 after ROSC.RESULTS:Following ROSC,the serum LDH(607.0 U/L vs.286.5 U/L),lactate(5.0 mmol/L vs.2.0 mmol/L),pyruvate(178.0 μmol/L vs.70.9 μmol/L),and lactate/pyruvate ratio(34.1 vs.22.1) significantly increased and were higher in the non-survivors than in the survivors on admission(all P<0.05).Moreover,the serum LDH,pyruvate,IL-6,APACHE II score,and SOFA score on days 1,3 and 7 after ROSC were significantly associated with 28-day poor neurological prognosis and 28-day all-cause mortality(all P<0.05).The serum LDH concentration on day 1 after ROSC had an area under the receiver operating characteristic curve(AUC) of 0.904 [95% confidence interval [95% CI]:0.851–0.957]) with 96.8% specificity for predicting 28-day neurological prognosis and an AUC of 0.950(95% CI:0.911–0.989) with 94.7% specificity for predicting 28-day all-cause mortality,which was the highest among the glucose metabolic reprogramming-related parameters tested.CONCLUSION:Serum parameters related to glucose metabolic reprogramming were significantly increased after ROSC.Increased serum LDH and pyruvate levels,and lactate/pyruvate ratio may be associated with 28-day poor neurological prognosis and all-cause mortality after ROSC,and the predictive eflcacy of LDH during the first week was superior to others.展开更多
Background:Hepatocellular carcinoma(HCC)is a common malignant tumor with poor prognosis and high mortality worldwide.Although cystathionine-gamma-lyase(CSE)plays an important role in the development of multiple tumors...Background:Hepatocellular carcinoma(HCC)is a common malignant tumor with poor prognosis and high mortality worldwide.Although cystathionine-gamma-lyase(CSE)plays an important role in the development of multiple tumors,the clinical implication and potential mechanisms of CSE in HCC development remain elusive.Methods:In our study,the CSE expression in HCC was analyzed in Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)datasets and further confirmed by RT-qPCR and immunohistochemistry assays in HCC samples.Furthermore,the associations between CSE expression and HCC malignancy as well as survival were analyzed in GSE14520 and validated in HCC patients.Finally,the biological functions of CSE in HCC cells was assessed by CCK-8,flow cytometry and Western blotting.Results:Lower transcriptional and proteomic CSE expressions were found in HCC tissues in contrast to adjacent normal tissues.Decreased CSE mRNA expression was significantly associated with advanced clinicopathological features and poor outcomes in HCC patients from public database and our cohort.Following univariate and multivariate analyses of GSE14520 data showed that CSE expression was an independent prognostic indicator for the overall survival(OS)and recurrence-free survival(RFS)of HCC patients.In vitro experiments further explained that CSE might trigger HCC cell apoptosis by H2S.Conclusion:In summary,the present study identified the relationship between CSE expression and HCC malignancy as well as OS and RFS,indicating that CSE might be a potential prognostic biomarker and a novel therapeutic target for HCC.展开更多
Nicotinamide adenine dinucleotide(NAD+)plays an essential role in cellular metabolism,mitochondrial homeostasis,inflammation,and senescence.However,the role of NAD+-regulated genes,including coding and long non-coding...Nicotinamide adenine dinucleotide(NAD+)plays an essential role in cellular metabolism,mitochondrial homeostasis,inflammation,and senescence.However,the role of NAD+-regulated genes,including coding and long non-coding genes in cancer development is poorly understood.We constructed a prediction model based on the expression level of NAD+metabolism-related genes(NMRGs).Furthermore,we validated the expression of NMRGs in gastric cancer(GC)tissues and cell lines;additionally,β-nicotinamide mononucleotide(NMN),a precursor of NAD+,was used to treat the GC cell lines to analyze its effects on the expression level of NMRGs lncRNAs and cellular proliferation,cell cycle,apoptosis,and senescence-associated secretory phenotype(SASP).A total of 13 NMRGs-related lncRNAs were selected to construct prognostic risk signatures,and patients with high-risk scores had a poor prognosis.Some immune checkpoint genes were upregulated in the high-risk group.In addition,cell cycle,epigenetics,and senescence were significantly downregulated in the high-risk group.Notably,we found that the levels of immune cell infiltration,including CD8 T cells,CD4 naïve T cells,CD4 memory-activated T cells,B memory cells,and naïve B cells,were significantly associated with risk scores.Furthermore,the treatment of NMN showed increased proliferation of AGS and MKN45 cells.In addition,the expression of SASP factors(IL6,IL8,IL10,TGF-β,and TNF-α)was significantly decreased after NMN treatment.We conclude that the lncRNAs associated with NAD+metabolism can potentially be used as biomarkers for predicting clinical outcomes of GC patients.展开更多
Introduction: Maternal mortality constitutes a public health problem and its rate is an indicator of a country’s development. Among the causes of maternal and perinatal death, high blood pressure associated with preg...Introduction: Maternal mortality constitutes a public health problem and its rate is an indicator of a country’s development. Among the causes of maternal and perinatal death, high blood pressure associated with pregnancy occupies a significant part. It represents 5% of direct maternal deaths. Objective: to study the maternal and perinatal prognosis of high blood pressure during pregnancy in the Tenenkou reference health center in Mali. Methodology: This was a descriptive, analytical and retrospective cross-sectional study over a period of twelve months from January 1, 2021 to December 31, 2021 and involving 144 cases of high blood pressure associated with pregnancy. Results: We obtained a frequency of 11.75%. The majority of patients 70.9% were aged between 20 - 35 years. The important risk factor found was young age. During our study, 46.5% of patients had performed at least one CPN and only 13.9% performed 04 CPN. Pre-eclampsia was the most common type of high blood pressure during pregnancy, i.e. 61.1%. Eclampsia and retroplacental hematoma were the most common maternal complications, respectively 27.8% and 11.1%. The most common fetal complications were premature births and fetal distress with 20.9% and 17.4% respectively. Conclusion: Hypertension associated with pregnancy still remains a major cause of maternal-fetal morbidity and mortality in our context where diagnosis is often late. The main clinical form was preeclampsia. Eclampsia and retroplacental hematoma were the most frequent maternal complications. Fetal complications were mainly prematurity and fetal distress.展开更多
Introduction: Acute obstructive renal failure (AORF) is a frequent clinical situation, secondary to obstruction of the urinary excretory tract. Whatever the cause, urinary tract obstruction suddenly opposes glomerular...Introduction: Acute obstructive renal failure (AORF) is a frequent clinical situation, secondary to obstruction of the urinary excretory tract. Whatever the cause, urinary tract obstruction suddenly opposes glomerular filtration and is responsible for tubulointerstitial lesions. It accounts for 10% of acute renal failure (ARF). The aim of this study was to identify the causes and prognosis of cases of acute obstructive renal failure managed at the Centre National d’hémodialyse Donka. Material and Methods: This was a prospective descriptive study lasting 6 months, from September 1, 2022 to February 29, 2023. All patients undergoing haemodialysis for acute obstructive renal failure who agreed to participate in the study and whose medical records were complete were included. Results: During the course of the study, we registered 97 haemodialysis patients, including 20 cases (20.62%) of acute obstructive renal failure. The mean age of the patients was 57.8 ± 10.54 years, with a male predominance of 11 cases (55%) and a sex ratio of 1.22. The reasons for consultation were dominated by physical asthenia 11 cases (55%), lumbar pain 9 cases (50%), vomiting 6 cases (30%) and acute urine retention 6 cases (30%). Arterial hypertension 16 cases (80%) and urinary tract infection 10 cases (50%) were the most common antecedents. The etiologies of RAOI were dominated by lithiasis 10 cases (50%), neoplasia 6 cases (30%) and benign prostatic hypertrophy 3 cases (15%). mean creatinine was 1267.60 ± 710.76 μmol/l with extremes of 243 μmol/l and 2822 μmol/l, mean urea was 39.56 ± 18.36, hyperkalemia in 14 cases (70%) and hyponatremia in 8 cases (40%). After hemodialysis, 9 cases (45%) recovered renal function, 4 cases (20%) became chronic and 7 cases (35%) died. Conclusion: The frequency of AKI remains non-negligible in our department, and early detection and prompt management would considerably reduce the morbidity and mortality associated with this pathology.展开更多
Background:Although it has been established that the human Solute Carrier Family 22(SLC22)functions as a cationic transporter,influencing cellular biological metabolism by modulating the uptake of various cations,its ...Background:Although it has been established that the human Solute Carrier Family 22(SLC22)functions as a cationic transporter,influencing cellular biological metabolism by modulating the uptake of various cations,its impact on cancer prognosis remains unclear.Methods:We conducted a comprehensive analysis utilizing data from The Cancer Genome Atlas(TCGA)and other databases to assess the prognostic value and functional implications across various tumors.Silence of SLC22A1 RNA in glioma U251 cells was performed to access the impact of SLC22A1 on lowergrade glioma(LGG)progression.Results:Our findings demonstrated a significant correlation between SLC22A1 expression and the survival time of patients with various cancers(p<0.05).Importantly,we found the potential involvement of SLC22A1 in occurrence and progress of certain cancers,with a pronounced impact on LGG.Further examination of the SLC22A1-LGG relationship revealed its status as an independent risk factor for LGG,suggesting its potential involvement in regulating diverse immune pathways and metabolic activities.Chinese Glioma Genome Atlas(CGGA)data supported the reliability of the risk score as a prognostic and recurrence indicator,emphasizing the accuracy of the nomograph(1,3,and 5-year-AUC>0.8).Cell proliferation and clone formation experiment proved that decreased expression of SLC22A1 in glioma U251 cells inhibited glioma cell growth.Conclusion:Our findings suggest SLC22A1 has huge prospects as a promising biomarker and therapeutic target for LGG prognosis.SLC22A1 has only been proved to support cellular function previously.Our findings demonstrated a robust connection between the tumor microenvironment and functional proteins that maintain basal cell metabolism,which gifts unique tumor immune characteristics of gliomas.Additionally,we provide a highly practical prediction model for estimating the survival rate of LGG patients.展开更多
Oxidative stress(OS)is intimately associated with tumorigenesis and has been considered a potential therapeutic strategy.However,the OS-associated therapeutic target for esophageal squamous cell carcinoma(ESCC)remains...Oxidative stress(OS)is intimately associated with tumorigenesis and has been considered a potential therapeutic strategy.However,the OS-associated therapeutic target for esophageal squamous cell carcinoma(ESCC)remains unconfirmed.In our study,gene expression data of ESCC and clinical information from public databases were downloaded.Through LASSO-Cox regression analysis,a risk score(RS)signature map of prognosis was constructed and performed external verification with the GSE53625 cohort.The ESTIMATE,xCell,CIBERSORT,TIMER,and ImmuCellAI algorithms were employed to analyze infiltrating immune cells and generate an immune microenvironment(IM).Afterward,functional enrichment analysis clarified the underlying mechanism of the model.Nomogram was utilized for forecasting the survival rate of individual ESCC cases.As a result,we successfully constructed an OS-related genes(OSRGs)model and found that the survival rate of high-risk groups was lower than that of low-risk groups.The AUC of the ROC verified the strong prediction performance of the signal in these two cohorts further.According to independent prognostic analysis,the RS was identified as an independent risk factor for ESCC.The nomogram and follow-up data revealed that the RS possesses favorable predictive value for the prognosis of ESCC patients.qRT-PCR detection demonstrated increased expression of MPC1,COX6C,CYB5R3,CASP7,and CYCS in esophageal cancer patients.In conclusion,we have constructed an OSRGs model for ESCC to predict patients’prognosis,offering a novel insight into the potential application of the OSRGs model in ESCC.展开更多
Hepatocellular carcinoma(HCC) is considered the fifth most prevalent cancer among all types of cancers and has the third most morbidity value. It has the most frequent duplication time and a high recurrence rate. Rece...Hepatocellular carcinoma(HCC) is considered the fifth most prevalent cancer among all types of cancers and has the third most morbidity value. It has the most frequent duplication time and a high recurrence rate. Recently, the most unique technique used is liquid biopsies, which carry many markers;the most prominent is circulating tumor DNA(ctDNA). Varied methods are used to investigate ctDNA, including various forms of polymerase chain reaction(PCR) [emulsion PCR(ePCR), digital PCR(dPCR), and bead, emulsion, amplification, magnetic(BEAMing) PCR]. Hence ctDNA is being recognized as a potential biomarker that permits early cancer detection,treatment monitoring, and predictive data on tumor burden are subjective to therapy or surgery. Numerous ctDNA biomarkers have been investigated based on their alterations such as 1) single nucleotide variations(either insertion or deletion of a nucleotide) markers including TP53, KRAS, and CCND1;2) copy number variations which include markers such as CDK6, EFGR, MYC and BRAF;3) DNA methylation(RASSF1A, SEPT9, KMT2C and CCNA2);4) homozygous mutation includes ctDNA markers as CDKN2A, AXIN1;and 5) gain or loss of function of the genes, particularly for HCC. Various researchers have conducted many studies and gotten fruitful results.Still, there are some drawbacks to ctDNA namely low quantity, fragment heterogeneity, less stability, limited mutant copies and standards, and differential sensitivity. However, plenty of investigations demonstrate ctDNA's significance as a polyvalent biomarker for cancer and can be viewed as a future diagnostic, prognostic and therapeutic agent. This article overviews many conditions in genetic changes linked to the onset and development of HCC, such as dysregulated signaling pathways, somatic mutations, single-nucleotide polymorphisms, and genomic instability. Additionally, efforts are also made to develop treatments for HCC that are molecularly targeted and to unravel some of the genetic pathways that facilitate its early identification.展开更多
BACKGROUND Gastric cancer has a high incidence and fatality rate,and surgery is the preferred course of treatment.Nonetheless,patient survival rates are still low,and the incidence of major postoperative complications...BACKGROUND Gastric cancer has a high incidence and fatality rate,and surgery is the preferred course of treatment.Nonetheless,patient survival rates are still low,and the incidence of major postoperative complications cannot be disregarded.The systemic inflammatory response,nutritional level,and coagulation status are key factors affecting the postoperative recovery and prognosis of gastric cancer patients.The systemic inflammatory response index(SIRI)and the albumin fibrinogen ratio(AFR)are two valuable comprehensive indicators of the severity and prognosis of systemic inflammation in various medical conditions.AIM To assess the clinical importance and prognostic significance of the SIRI scores and the AFR on early postoperative outcomes in patients undergoing radical gastric cancer surgery.METHODS We conducted a retrospective analysis of the clinicopathological characteristics and relevant laboratory indices of 568 gastric cancer patients from January 2018 to December 2019.We calculated and compared two indicators of inflammation and then examined the diagnostic ability of combined SIRI and AFR values for serious early postoperative complications.We scored the patients and categorized them into three groups based on their SIRI and AFR levels.COX analysis was used to compare the three groups of patients the prognostic value of various preoperative SIRI-AFR scores for 5-year overall survival(OS)and disease-free survival(DFS).RESULTS SIRI-AFR scores were an independent risk factor for prognosis[OS:P=0.004;hazards ratio(HR)=3.134;DFS:P<0.001;HR=3.543]and had the highest diagnostic power(area under the curve:0.779;95%confidence interval:0.737-0.820)for early serious complications in patients with gastric cancer.The tumor-node-metastasis stage(P=0.001),perioperative transfusion(P=0.044),positive carcinoembryonic antigen(P=0.014)findings,and major postoperative complications(P=0.011)were factors associated with prognosis.CONCLUSION Preoperative SIRI and AFR values were significantly associated with early postoperative survival and the occurrence of severe complications in gastric cancer patients.展开更多
BACKGROUND Gastric cancer(GC)is a highly aggressive malignancy with a heterogeneous nature,which makes prognosis prediction and treatment determination difficult.Inflammation is now recognized as one of the hallmarks ...BACKGROUND Gastric cancer(GC)is a highly aggressive malignancy with a heterogeneous nature,which makes prognosis prediction and treatment determination difficult.Inflammation is now recognized as one of the hallmarks of cancer and plays an important role in the aetiology and continued growth of tumours.Inflammation also affects the prognosis of GC patients.Recent reports suggest that a number of inflammatory-related biomarkers are useful for predicting tumour prognosis.However,the importance of inflammatory-related biomarkers in predicting the prognosis of GC patients is still unclear.AIM To investigate inflammatory-related biomarkers in predicting the prognosis of GC patients.was constructed using the least absolute shrinkage and selection operator Cox regression model based on the GEO database.GC patients from the GSE26253 cohort were used for validation.Univariate and multivariate Cox analyses were used to determine the independent prognostic factors,and a prognostic nomogram was established.The calibration curve and the area under the curve based on receiver operating characteristic analysis were utilized to evaluate the predictive value of the nomogram.The decision curve analysis results were plotted to quantify and assess the clinical value of the nomogram.Gene set enrichment analysis was performed to explore the potential regulatory pathways involved.The relationship between tumour immune infiltration status and risk score was analysed via Tumour Immune Estimation Resource and CIBERSORT.Finally,we analysed the association between risk score and patient sensitivity to commonly used chemotherapy and targeted therapy agents.RESULTS A prognostic model consisting of three inflammatory-related genes(MRPS17,GUF1,and PDK4)was constructed.Independent prognostic analysis revealed that the risk score was a separate prognostic factor in GC patients.According to the risk score,GC patients were stratified into high-and low-risk groups,and patients in the high-risk group had significantly worse prognoses according to age,sex,TNM stage and Lauren type.Consensus clustering identified three subtypes of inflammation that could predict GC prognosis more accurately than traditional grading and staging.Finally,the study revealed that patients in the low-risk group were more sensitive to certain drugs than were those in the high-risk group,indicating a link between inflammation-related genes and drug sensitivity.CONCLUSION In conclusion,we established a novel three-gene prognostic signature that may be useful for predicting the prognosis and personalizing treatment decisions of GC patients.展开更多
Introduction: Retroplacental haematoma (RPH) is a very serious complication of pregnancy, with life-threatening consequences for both the mother and foetus. The aim of this study is to determine the incidence and epid...Introduction: Retroplacental haematoma (RPH) is a very serious complication of pregnancy, with life-threatening consequences for both the mother and foetus. The aim of this study is to determine the incidence and epidemiological characteristics of patients with retroplacental haematoma (RPH) and describe the maternal-foetal complications at Bouaké University Hospital. Methods: This was a cross-sectional prospective, descriptive and analytical study carried out at Bouaké University Hospital over a period of 3 years, from January 1, 2019 to December 31, 2021. All parturients with RPH whose delivery took place at the hospital were included in the study. Data were entered and analysed using EPI INFO software version 7.2.2.6. Results: We recorded 2,0959 deliveries, including 202 cases of RPH, representing an incidence of 0.96%. The 21 to 35 age group accounted for 64.4%, multigestas and large multigestas accounted for 58.5% and multiparas accounted for 41.6%. The main signs on clinical examination were metrorrhagia (100%), arterial hypertension (84.6%) and cervical cerclage (79.7%). Preeclampsia accounted for 50% of per-gestational pathologies. Maternal mortality was 12.9%. Morbidity was dominated by anaemia in 64.1%, followed by disseminated intravascular coagulation (DIC) in 21.8%, and the factors associated with this maternal prognosis were multiple gestations, multiparity, Sher grade IIIb and the occurrence of complications such as DIC, shock, renal complications and HELLP syndrome. Neonatal mortality was 79.2%, and the factors associated with these fetal prognoses were cup size ≥ 5 cm and hematoma weight ≥ 500 g. Conclusion: Better screening of at-risk populations, early diagnosis and treatment in an organised and equipped medical and surgical facility would improve prognosis.展开更多
BACKGROUND Heat shock proteins(HSPs)are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overex-pressed in many cancers.The prognostic signific...BACKGROUND Heat shock proteins(HSPs)are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overex-pressed in many cancers.The prognostic significance of HSPs and their regulatory factors,such as heat shock factor 1(HSF1)and CHIP,are poorly understood.AIM To investigate the relationship between HSP expression and prognosis in esophageal and esophagogastric cancer.METHODS A systematic review was conducted in accordance with PRISMA recommend-ations(PROSPERO:CRD42022370653),on Embase,PubMed,Cochrane,and LILACS.Cohort,case-control,and cross-sectional studies of patients with eso-phagus or esophagogastric cancer were included.HSP-positive patients were compared with HSP-negative,and the endpoints analyzed were lymph node metastasis,tumor depth,distant metastasis,and overall survival(OS).HSPs were stratified according to the HSP family,and the summary risk difference(RD)was calculated using a random-effect model.RESULTS The final selection comprised 27 studies,including esophageal squamous cell carcinoma(21),esophagogastric adenocarcinoma(5),and mixed neoplasms(1).The pooled sample size was 3465 patients.HSP40 and 60 were associated with a higher 3-year OS[HSP40:RD=0.22;95%confidence interval(CI):0.09-0.35;HSP60:RD=0.33;95%CI:0.17-0.50],while HSF1 was associated with a poor 3-year OS(RD=-0.22;95%CI:-0.32 to-0.12).The other HSP families were not associated with long-term survival.HSF1 was associated with a higher probability of lymph node metastasis(RD=-0.16;95%CI:-0.29 to-0.04).HSP40 was associated with a lower probability of lymph node dissemination(RD=0.18;95%CI:0.03-0.33).The expression of other HSP families was not significantly related to tumor depth and lymph node or distant metastasis.CONCLUSION The expression levels of certain families of HSP,such as HSP40 and 60 and HSF1,are associated with long-term survival and lymph node dissemination in patients with esophageal and esophagogastric cancer.展开更多
BACKGROUND There is currently a shortage of accurate,efficient,and precise predictive instruments for rectal neuroendocrine neoplasms(NENs).AIM To develop a predictive model for individuals with rectal NENs(R-NENs)usi...BACKGROUND There is currently a shortage of accurate,efficient,and precise predictive instruments for rectal neuroendocrine neoplasms(NENs).AIM To develop a predictive model for individuals with rectal NENs(R-NENs)using data from a large cohort.METHODS Data from patients with primary R-NENs were retrospectively collected from 17 large-scale referral medical centers in China.Random forest and Cox proportional hazard models were used to identify the risk factors for overall survival and progression-free survival,and two nomograms were constructed.RESULTS A total of 1408 patients with R-NENs were included.Tumor grade,T stage,tumor size,age,and a prognostic nutritional index were important risk factors for prognosis.The GATIS score was calculated based on these five indicators.For overall survival prediction,the respective C-indexes in the training set were 0.915(95%confidence interval:0.866-0.964)for overall survival prediction and 0.908(95%confidence interval:0.872-0.944)for progression-free survival prediction.According to decision curve analysis,net benefit of the GATIS score was higher than that of a single factor.The time-dependent area under the receiver operating characteristic curve showed that the predictive power of the GATIS score was higher than that of the TNM stage and pathological grade at all time periods.CONCLUSION The GATIS score had a good predictive effect on the prognosis of patients with R-NENs,with efficacy superior to that of the World Health Organization grade and TNM stage.展开更多
BACKGROUND Gastric cancer(GC)has a high mortality rate worldwide.Despite significant progress in GC diagnosis and treatment,the prognosis for affected patients still remains unfavorable.AIM To identify important candi...BACKGROUND Gastric cancer(GC)has a high mortality rate worldwide.Despite significant progress in GC diagnosis and treatment,the prognosis for affected patients still remains unfavorable.AIM To identify important candidate genes related to the development of GC and iden-tify potential pathogenic mechanisms through comprehensive bioinformatics analysis.METHODS The Gene Expression Omnibus database was used to obtain the GSE183136 dataset,which includes a total of 135 GC samples.The limma package in R software was employed to identify differentially expressed genes(DEGs).Thereafter,enrichment analyses of Gene Ontology(GO)terms and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways were performed for the gene modules using the clusterProfile package in R software.The protein-protein interaction(PPI)networks of target genes were constructed using STRING and visualized by Cytoscape software.The common hub genes that emerged in the cohort of DEGs that was retrieved from the GEPIA database were then screened using a Venn Diagram.The expression levels of these overlapping genes in stomach adenocarcinoma samples and non-tumor samples and their association with prognosis in GC patients were also obtained from the GEPIA database and Kaplan-Meier curves.Moreover,real-time quantitative polymerase chain reaction(RT-qPCR)and western blotting were performed to determine the mRNA and protein levels of glutamic-pyruvic transaminase(GPT)in GC and normal immortalized cell lines.In addition,cell viability,cell cycle distribution,migration and invasion were evaluated by cell counting kit-8,flow cytometry and transwell assays.Furthermore,we also conducted a retrospective analysis on 70 GC patients diagnosed and surgically treated in Wenzhou Central Hospital,Dingli Clinical College of Wenzhou Medical University,The Second Affiliated Hospital of Shanghai University between January 2017 to December 2020.The tumor and adjacent normal samples were collected from the patients to determine the potential association between the expression level of GPT and the clinical as well as pathological features of GC patients.RESULTS We selected 19214 genes from the GSE183136 dataset,among which there were 250 downregulated genes and 401 upregulated genes in the tumor samples of stage III-IV in comparison to those in tumor samples of stage I-II with a P-value<0.05.In addition,GO and KEGG results revealed that the various upregulated DEGs were mainly enriched in plasma membrane and neuroactive ligand-receptor interaction,whereas the downregulated DEGs were primarily enriched in cytosol and pancreatic secretion,vascular smooth muscle contraction and biosynthesis of the different cofactors.Furthermore,PPI networks were constructed based on the various upregulated and downregulated genes,and there were a total 15 upregulated and 10 downregulated hub genes.After a comprehensive analysis,several hub genes,including runt-related transcription factor 2(RUNX2),salmonella pathogenicity island 1(SPI1),lysyl oxidase(LOX),fibrillin 1(FBN1)and GPT,displayed prognostic values.Interestingly,it was observed that GPT was downregulated in GC cells and its upregulation could suppress the malignant phenotypes of GC cells.Furthermore,the expression level of GPT was found to be associated with age,lymph node metastasis,pathological staging and distant metastasis(P<0.05).CONCLUSION RUNX2,SPI1,LOX,FBN1 and GPT were identified key hub genes in GC by bioinformatics analysis.GPT was significantly associated with the prognosis of GC,and its upregulation can effectively inhibit the proliferative,migrative and invasive capabilities of GC cells.展开更多
BACKGROUND Liver cancer is one of the deadliest malignant tumors worldwide.Immunotherapy has provided hope to patients with advanced liver cancer,but only a small fraction of patients benefit from this treatment due t...BACKGROUND Liver cancer is one of the deadliest malignant tumors worldwide.Immunotherapy has provided hope to patients with advanced liver cancer,but only a small fraction of patients benefit from this treatment due to individual differences.Identifying immune-related gene signatures in liver cancer patients not only aids physicians in cancer diagnosis but also offers personalized treatment strategies,thereby improving patient survival rates.Although several methods have been developed to predict the prognosis and immunotherapeutic efficacy in patients with liver cancer,the impact of cell-cell interactions in the tumor microenvir-onment has not been adequately considered.AIM To identify immune-related gene signals for predicting liver cancer prognosis and immunotherapy efficacy.METHODS Cell grouping and cell-cell communication analysis were performed on single-cell RNA-sequencing data to identify highly active cell groups in immune-related pathways.Highly active immune cells were identified by intersecting the highly active cell groups with B cells and T cells.The significantly differentially expressed genes between highly active immune cells and other cells were subsequently selected as features,and a least absolute shrinkage and selection operator(LASSO)regression model was constructed to screen for diagnostic-related features.Fourteen genes that were selected more than 5 times in 10 LASSO regression experiments were included in a multivariable Cox regression model.Finally,3 genes(stathmin 1,cofilin 1,and C-C chemokine ligand 5)significantly associated with survival were identified and used to construct an immune-related gene signature.RESULTS The immune-related gene signature composed of stathmin 1,cofilin 1,and C-C chemokine ligand 5 was identified through cell-cell communication.The effectiveness of the identified gene signature was validated based on experi-mental results of predictive immunotherapy response,tumor mutation burden analysis,immune cell infiltration analysis,survival analysis,and expression analysis.CONCLUSION The findings suggest that the identified gene signature may contribute to a deeper understanding of the activity patterns of immune cells in the liver tumor microenvironment,providing insights for personalized treatment strategies.展开更多
基金Supported by Suzhou Science and Technology Project,No.SYS2019053.
文摘BACKGROUND Prostate cancer(PCa)is a widespread malignancy,predominantly affecting elderly males,and current methods for diagnosis and treatment of this disease continue to fall short.The marker Ki-67(MKI67)has been previously demonstrated to correlate with the proliferation and metastasis of various cancer cells,including those of PCa.Hence,verifying the association between MKI67 and the diagnosis and prognosis of PCa,using bioinformatics databases and clinical data analysis,carries significant clinical implications.AIM To explore the diagnostic and prognostic efficacy of antigens identified by MKI67 expression in PCa.METHODS For cohort 1,the efficacy of MKI67 diagnosis was evaluated using data from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases.For cohort 2,the diagnostic and prognostic power of MKI67 expression was further validated using data from 271 patients with clinical PCa.RESULTS In cohort 1,MKI67 expression was correlated with prostate-specific antigen(PSA),Gleason Score,T stage,and N stage.The receiver operating characteristic(ROC)curve showed a strong diagnostic ability,and the Kaplan-Meier method demonstrated that MKI67 expression was negatively associated with the progression-free interval(PFI).The time-ROC curve displayed a weak prognostic capability for MKI67 expression in PCa.In cohort 2,MKI67 expression was significantly related to the Gleason Score,T stage,and N stage;however,it was negatively associated with the PFI.The time-ROC curve revealed the stronger prognostic capability of MKI67 in patients with PCa.Multivariate COX regression analysis was performed to select risk factors,including PSA level,N stage,and MKI67 expression.A nomogram was established to predict the 3-year PFI.CONCLUSION MKI67 expression was positively associated with the Gleason Score,T stage,and N stage and showed a strong diagnostic and prognostic ability in PCa.
基金The Science and Technology Commission of Shanxi province,No.201901D111428.
文摘BACKGROUND Ferroptosis has recently been associated with multiple degenerative diseases.Ferroptosis induction in cancer cells is a feasible method for treating neoplastic diseases.However,the association of iron proliferation-related genes with prognosis in HER2+breast cancer(BC)patients is unclear.AIM To identify and evaluate fresh ferroptosis-related biomarkers for HER2+BC.METHODS First,we obtained the mRNA expression profiles and clinical information of HER2+BC patients from the TCGA and METABRIC public databases.A four gene prediction model comprising PROM2,SLC7A11,FANCD2,and FH was subsequently developed in the TCGA cohort and confirmed in the METABRIC cohort.Patients were stratified into high-risk and low-risk groups based on their median risk score,an independent predictor of overall survival(OS).Based on these findings,immune infiltration,mutations,and medication sensitivity were analyzed in various risk groupings.Additionally,we assessed patient prognosis by combining the tumor mutation burden(TMB)with risk score.Finally,we evaluated the expression of critical genes by analyzing single-cell RNA sequencing(scRNA-seq)data from malignant vs normal epithelial cells.RESULTS We found that the higher the risk score was,the worse the prognosis was(P<0.05).We also found that the immune cell infiltration,mutation,and drug sensitivity were different between the different risk groups.The highrisk subgroup was associated with lower immune scores and high TMB.Moreover,we found that the combination of the TMB and risk score could stratify patients into three groups with distinct prognoses.HRisk-HTMB patients had the worst prognosis,whereas LRisk-LTMB patients had the best prognosis(P<0.0001).Analysis of the scRNAseq data showed that PROM2,SLC7A11,and FANCD2 were significantly differentially expressed,whereas FH was not,suggesting that these genes are expressed mainly in cancer epithelial cells(P<0.01).CONCLUSION Our model helps guide the prognosis of HER2+breast cancer patients,and its combination with the TMB can aid in more accurate assessment of patient prognosis and provide new ideas for further diagnosis and treatment.
基金National High Level Hospital Clinical Research Funding,No.2022-PUMCH-B-022CAMS Innovation Fund for Medical Sciences,No.CIFMS 2021-1-I2M-003and Undergraduate Innovation Program,No.2023zglc06076.
文摘BACKGROUND Eosinophilic gastroenteritis(EGE)is a chronic recurrent disease with abnormal eosinophilic infiltration in the gastrointestinal tract.Glucocorticoids remain the most common treatment method.However,disease relapse and glucocorticoid dependence remain notable problems.To date,few studies have illuminated the prognosis of EGE and risk factors for disease relapse.AIM To describe the clinical characteristics of EGE and possible predictive factors for disease relapse based on long-term follow-up.METHODS This was a retrospective cohort study of 55 patients diagnosed with EGE admitted to one medical center between 2013 and 2022.Clinical records were collected and analyzed.Kaplan-Meier curves and log-rank tests were conducted to reveal the risk factors for long-term relapse-free survival(RFS).RESULTS EGE showed a median onset age of 38 years and a slight female predominance(56.4%).The main clinical symptoms were abdominal pain(89.1%),diarrhea(61.8%),nausea(52.7%),distension(49.1%)and vomiting(47.3%).Forty-three(78.2%)patients received glucocorticoid treatment,and compared with patients without glucocorticoid treatments,they were more likely to have elevated serum immunoglobin E(IgE)(86.8%vs 50.0%,P=0.022)and descending duodenal involvement(62.8%vs 27.3%,P=0.046)at diagnosis.With a median follow-up of 67 mo,all patients survived,and 56.4%had at least one relapse.Six variables at baseline might have been associated with the overall RFS rate,including age at diagnosis<40 years[hazard ratio(HR)2.0408,95%confidence interval(CI):1.0082–4.1312,P=0.044],body mass index(BMI)>24 kg/m^(2)(HR 0.3922,95%CI:0.1916-0.8027,P=0.014),disease duration from symptom onset to diagnosis>3.5 mo(HR 2.4725,95%CI:1.220-5.0110,P=0.011),vomiting(HR 3.1259,95%CI:1.5246-6.4093,P=0.001),total serum IgE>300 KU/L at diagnosis(HR 0.2773,95%CI:0.1204-0.6384,P=0.022)and glucocorticoid treatment(HR 6.1434,95%CI:2.8446-13.2676,P=0.003).CONCLUSION In patients with EGE,younger onset age,longer disease course,vomiting and glucocorticoid treatment were risk factors for disease relapse,whereas higher BMI and total IgE level at baseline were protective.
文摘Primary tumors of the central nervous system(CNS)are classified into over 100 different histological types.The most common type of glioma is derived from astrocytes,and the most invasive glioblastoma(WHO IV)accounts for over 57%of these tumors.Glioblastoma(GBM)is the most common and fatal tumor of the CNS,with strong growth and invasion capabilities,which makes complete surgical resection almost impossible.Despite various treatment methods such as surgery,radiotherapy,and chemotherapy,glioma is still an incurable disease,and the median survival time of patients with GBM is shorter than 15 months.Thus,molecular mechanisms of GBM characteristic invasive growth need to be clarified to improve the poor prognosis.Glutamate ionotropic receptor kainate type subunit 1(GRIK1)is essential for brain function and is involved in many mental and neurological diseases.However,GRIK1’s pathogenic roles and mechanisms in GBM are still unknown.Single-nuclear RNA sequencing of primary and recurrent GBM samples revealed that GRIK1 expression was noticeably higher in the recurrent samples.Moreover,immunohistochemical staining of an array of GBM samples showed that high levels of GRIK1 correlated with poor prognosis of GBM,consistent with The Cancer Genome Atlas database.Knockdown of GRIK1 retarded GBM cells growth,migration,and invasion.Taken together,these findings show that GRIK1 is a unique and important component in the development of GBM and may be considered as a biomarker for the diagnosis and therapy in individuals with GBM.
基金Supported by National Natural Science Foundation of China,No.82172737Shanghai Science and Technology Development Funds(Shanghai Sailing Program),No.22YF1427600。
文摘BACKGROUND Lactate,previously considered a metabolic byproduct,is pivotal in cancer progression and maintaining the immunosuppressive tumor microenvironment.Further investigations confirmed that lactate is a primary regulator,introducing recently described post-translational modifications of histone and non-histone proteins,termed lysine lactylation.Pancreatic adenocarcinomas are characterized by increased glycolysis and lactate accumulation.However,our understanding of lactylation-related genes in pancreatic adenocarcinomas remains limited.AIM To construct a novel lactylation-related gene signature to predict the survival of patients with pancreatic cancer.METHODS RNA-seq and clinical data of pancreatic adenocarcinoma(PDAC)were obtained from the GTEx(Genotype-Tissue Expression)and TCGA(The Cancer Genome Atlas)databases via Xena Explorer,and GSE62452 datasets from GEO.Data on lactylation-related genes were obtained from publicly available sources.Differential expressed genes(DEGs)were acquired by using R package“DESeq2”in R.Univariate COX regression analysis,LASSO Cox and multivariate Cox regressions were produced to construct the lactylation-related prognostic model.Further analyses,including functional enrichment,ESTIMATE,and CIBERSORT,were performed to analyze immune status and treatment responses in patients with pancreatic cancer.PDAC and normal human cell lines were subjected to western blot analysis under lactic acid intervention;two PDAC cell lines with the most pronounced lactylation were selected.Subsequently,RT-PCR was employed to assess the expression of LRGs genes;SLC16A1,which showed the highest expression,was selected for further investigation.SLC16A1-mediated lactylation was analyzed by immunofluorescence,lactate production analysis,colony formation,transwell,and wound healing assays to investigate its role in promoting the proliferation and migration of PDAC cells.In vivo validation was performed using an established tumor model.RESULTS In this study,we successfully identified 10 differentially expressed lactylation-related genes(LRGs)with prognostic value.Subsequently,a lactylation-related signature was developed based on five OS-related lactylationrelated genes(SLC16A1,HLA-DRB1,KCNN4,KIF23,and HPDL)using Lasso Cox hazard regression analysis.Subsequently,we evaluated the clinical significance of the lactylation-related genes in pancreatic adenocarcinoma.A comprehensive examination of infiltrating immune cells and tumor mutation burden was conducted across different subgroups.Furthermore,we demonstrated that SLC16A1 modulates lactylation in pancreatic cancer cells through lactate transport.Both in vivo and in vitro experiments showed that decreasing SLC16A1 Level and its lactylation significantly inhibited tumor progression,indicating the potential of targeting the SLC16A1/Lactylation-associated signaling pathway as a therapeutic strategy against pancreatic adenocarcinoma.CONCLUSION We constructed a novel lactylation-related prognostic signature to predict OS,immune status,and treatment response of patients with pancreatic adenocarcinoma,providing new strategic directions and antitumor immunotherapies.
基金funded by the Shenzhen Science and Technology Program (JCYJ20230807112007014)Shenzhen Key Medical Discipline Construction Fund (SZXK046)。
文摘BACKGROUND:We aimed to observe the dynamic changes in glucose metabolic reprogrammingrelated parameters and their ability to predict neurological prognosis and all-cause mortality in cardiac arrest patients after the restoration of spontaneous circulation(ROSC).METHODS:Adult cardiac arrest patients after ROSC who were admitted to the emergency or cardiac intensive care unit of the First Aflliated Hospital of Dalian Medical University from August 1,2017,to May 30,2021,were enrolled.According to 28-day survival,the patients were divided into a non-survival group(n=82) and a survival group(n=38).Healthy adult volunteers(n=40) of similar ages and sexes were selected as controls.The serum levels of glucose metabolic reprogrammingrelated parameters(lactate dehydrogenase [LDH],lactate and pyruvate),neuron-specific enolase(NSE) and interleukin 6(IL-6) were measured on days 1,3,and 7 after ROSC.The Acute Physiology and Chronic Health Evaluation II(APACHE II) score and Sequential Organ Failure Assessment(SOFA) score were calculated.The Cerebral Performance Category(CPC) score was recorded on day 28 after ROSC.RESULTS:Following ROSC,the serum LDH(607.0 U/L vs.286.5 U/L),lactate(5.0 mmol/L vs.2.0 mmol/L),pyruvate(178.0 μmol/L vs.70.9 μmol/L),and lactate/pyruvate ratio(34.1 vs.22.1) significantly increased and were higher in the non-survivors than in the survivors on admission(all P<0.05).Moreover,the serum LDH,pyruvate,IL-6,APACHE II score,and SOFA score on days 1,3 and 7 after ROSC were significantly associated with 28-day poor neurological prognosis and 28-day all-cause mortality(all P<0.05).The serum LDH concentration on day 1 after ROSC had an area under the receiver operating characteristic curve(AUC) of 0.904 [95% confidence interval [95% CI]:0.851–0.957]) with 96.8% specificity for predicting 28-day neurological prognosis and an AUC of 0.950(95% CI:0.911–0.989) with 94.7% specificity for predicting 28-day all-cause mortality,which was the highest among the glucose metabolic reprogramming-related parameters tested.CONCLUSION:Serum parameters related to glucose metabolic reprogramming were significantly increased after ROSC.Increased serum LDH and pyruvate levels,and lactate/pyruvate ratio may be associated with 28-day poor neurological prognosis and all-cause mortality after ROSC,and the predictive eflcacy of LDH during the first week was superior to others.
基金This study was supported by Beijing Municipal Science&Technology Commission to Huiguo Ding(Z221100007422002)Beijing Hospitals Authority Youth Programme to Shanshan Wang(QML20211701).
文摘Background:Hepatocellular carcinoma(HCC)is a common malignant tumor with poor prognosis and high mortality worldwide.Although cystathionine-gamma-lyase(CSE)plays an important role in the development of multiple tumors,the clinical implication and potential mechanisms of CSE in HCC development remain elusive.Methods:In our study,the CSE expression in HCC was analyzed in Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)datasets and further confirmed by RT-qPCR and immunohistochemistry assays in HCC samples.Furthermore,the associations between CSE expression and HCC malignancy as well as survival were analyzed in GSE14520 and validated in HCC patients.Finally,the biological functions of CSE in HCC cells was assessed by CCK-8,flow cytometry and Western blotting.Results:Lower transcriptional and proteomic CSE expressions were found in HCC tissues in contrast to adjacent normal tissues.Decreased CSE mRNA expression was significantly associated with advanced clinicopathological features and poor outcomes in HCC patients from public database and our cohort.Following univariate and multivariate analyses of GSE14520 data showed that CSE expression was an independent prognostic indicator for the overall survival(OS)and recurrence-free survival(RFS)of HCC patients.In vitro experiments further explained that CSE might trigger HCC cell apoptosis by H2S.Conclusion:In summary,the present study identified the relationship between CSE expression and HCC malignancy as well as OS and RFS,indicating that CSE might be a potential prognostic biomarker and a novel therapeutic target for HCC.
基金supported by Zhengzhou Major Collaborative Innovation Project(No.18XTZX12003)Key Projects of Discipline Construction in Zhengzhou University(No.XKZDJC202001)+1 种基金National Key Research and Development Program in China(No.2020YFC2006100)Medical Service Capacity Improvement Project of Henan Province in China(Grant Number Yu Wei Medicine[2017]No.66).
文摘Nicotinamide adenine dinucleotide(NAD+)plays an essential role in cellular metabolism,mitochondrial homeostasis,inflammation,and senescence.However,the role of NAD+-regulated genes,including coding and long non-coding genes in cancer development is poorly understood.We constructed a prediction model based on the expression level of NAD+metabolism-related genes(NMRGs).Furthermore,we validated the expression of NMRGs in gastric cancer(GC)tissues and cell lines;additionally,β-nicotinamide mononucleotide(NMN),a precursor of NAD+,was used to treat the GC cell lines to analyze its effects on the expression level of NMRGs lncRNAs and cellular proliferation,cell cycle,apoptosis,and senescence-associated secretory phenotype(SASP).A total of 13 NMRGs-related lncRNAs were selected to construct prognostic risk signatures,and patients with high-risk scores had a poor prognosis.Some immune checkpoint genes were upregulated in the high-risk group.In addition,cell cycle,epigenetics,and senescence were significantly downregulated in the high-risk group.Notably,we found that the levels of immune cell infiltration,including CD8 T cells,CD4 naïve T cells,CD4 memory-activated T cells,B memory cells,and naïve B cells,were significantly associated with risk scores.Furthermore,the treatment of NMN showed increased proliferation of AGS and MKN45 cells.In addition,the expression of SASP factors(IL6,IL8,IL10,TGF-β,and TNF-α)was significantly decreased after NMN treatment.We conclude that the lncRNAs associated with NAD+metabolism can potentially be used as biomarkers for predicting clinical outcomes of GC patients.
文摘Introduction: Maternal mortality constitutes a public health problem and its rate is an indicator of a country’s development. Among the causes of maternal and perinatal death, high blood pressure associated with pregnancy occupies a significant part. It represents 5% of direct maternal deaths. Objective: to study the maternal and perinatal prognosis of high blood pressure during pregnancy in the Tenenkou reference health center in Mali. Methodology: This was a descriptive, analytical and retrospective cross-sectional study over a period of twelve months from January 1, 2021 to December 31, 2021 and involving 144 cases of high blood pressure associated with pregnancy. Results: We obtained a frequency of 11.75%. The majority of patients 70.9% were aged between 20 - 35 years. The important risk factor found was young age. During our study, 46.5% of patients had performed at least one CPN and only 13.9% performed 04 CPN. Pre-eclampsia was the most common type of high blood pressure during pregnancy, i.e. 61.1%. Eclampsia and retroplacental hematoma were the most common maternal complications, respectively 27.8% and 11.1%. The most common fetal complications were premature births and fetal distress with 20.9% and 17.4% respectively. Conclusion: Hypertension associated with pregnancy still remains a major cause of maternal-fetal morbidity and mortality in our context where diagnosis is often late. The main clinical form was preeclampsia. Eclampsia and retroplacental hematoma were the most frequent maternal complications. Fetal complications were mainly prematurity and fetal distress.
文摘Introduction: Acute obstructive renal failure (AORF) is a frequent clinical situation, secondary to obstruction of the urinary excretory tract. Whatever the cause, urinary tract obstruction suddenly opposes glomerular filtration and is responsible for tubulointerstitial lesions. It accounts for 10% of acute renal failure (ARF). The aim of this study was to identify the causes and prognosis of cases of acute obstructive renal failure managed at the Centre National d’hémodialyse Donka. Material and Methods: This was a prospective descriptive study lasting 6 months, from September 1, 2022 to February 29, 2023. All patients undergoing haemodialysis for acute obstructive renal failure who agreed to participate in the study and whose medical records were complete were included. Results: During the course of the study, we registered 97 haemodialysis patients, including 20 cases (20.62%) of acute obstructive renal failure. The mean age of the patients was 57.8 ± 10.54 years, with a male predominance of 11 cases (55%) and a sex ratio of 1.22. The reasons for consultation were dominated by physical asthenia 11 cases (55%), lumbar pain 9 cases (50%), vomiting 6 cases (30%) and acute urine retention 6 cases (30%). Arterial hypertension 16 cases (80%) and urinary tract infection 10 cases (50%) were the most common antecedents. The etiologies of RAOI were dominated by lithiasis 10 cases (50%), neoplasia 6 cases (30%) and benign prostatic hypertrophy 3 cases (15%). mean creatinine was 1267.60 ± 710.76 μmol/l with extremes of 243 μmol/l and 2822 μmol/l, mean urea was 39.56 ± 18.36, hyperkalemia in 14 cases (70%) and hyponatremia in 8 cases (40%). After hemodialysis, 9 cases (45%) recovered renal function, 4 cases (20%) became chronic and 7 cases (35%) died. Conclusion: The frequency of AKI remains non-negligible in our department, and early detection and prompt management would considerably reduce the morbidity and mortality associated with this pathology.
基金supported by National Natural Science Foundation of China(82160639)the Guizhou Provincial Science&Technology Program(QKHJC[2021]571)+2 种基金the Science&Technology Plan of Zunyi(ZSKHHZ[2020]87)the Xin Miao Foundation of Zunyi Medical University(QKPTRC[2019]-026)the PhD Start-Up Foundation of Zunyi Medical University(F-948).
文摘Background:Although it has been established that the human Solute Carrier Family 22(SLC22)functions as a cationic transporter,influencing cellular biological metabolism by modulating the uptake of various cations,its impact on cancer prognosis remains unclear.Methods:We conducted a comprehensive analysis utilizing data from The Cancer Genome Atlas(TCGA)and other databases to assess the prognostic value and functional implications across various tumors.Silence of SLC22A1 RNA in glioma U251 cells was performed to access the impact of SLC22A1 on lowergrade glioma(LGG)progression.Results:Our findings demonstrated a significant correlation between SLC22A1 expression and the survival time of patients with various cancers(p<0.05).Importantly,we found the potential involvement of SLC22A1 in occurrence and progress of certain cancers,with a pronounced impact on LGG.Further examination of the SLC22A1-LGG relationship revealed its status as an independent risk factor for LGG,suggesting its potential involvement in regulating diverse immune pathways and metabolic activities.Chinese Glioma Genome Atlas(CGGA)data supported the reliability of the risk score as a prognostic and recurrence indicator,emphasizing the accuracy of the nomograph(1,3,and 5-year-AUC>0.8).Cell proliferation and clone formation experiment proved that decreased expression of SLC22A1 in glioma U251 cells inhibited glioma cell growth.Conclusion:Our findings suggest SLC22A1 has huge prospects as a promising biomarker and therapeutic target for LGG prognosis.SLC22A1 has only been proved to support cellular function previously.Our findings demonstrated a robust connection between the tumor microenvironment and functional proteins that maintain basal cell metabolism,which gifts unique tumor immune characteristics of gliomas.Additionally,we provide a highly practical prediction model for estimating the survival rate of LGG patients.
基金Natural Science Foundation of Ningbo(Grant No.2021J261).
文摘Oxidative stress(OS)is intimately associated with tumorigenesis and has been considered a potential therapeutic strategy.However,the OS-associated therapeutic target for esophageal squamous cell carcinoma(ESCC)remains unconfirmed.In our study,gene expression data of ESCC and clinical information from public databases were downloaded.Through LASSO-Cox regression analysis,a risk score(RS)signature map of prognosis was constructed and performed external verification with the GSE53625 cohort.The ESTIMATE,xCell,CIBERSORT,TIMER,and ImmuCellAI algorithms were employed to analyze infiltrating immune cells and generate an immune microenvironment(IM).Afterward,functional enrichment analysis clarified the underlying mechanism of the model.Nomogram was utilized for forecasting the survival rate of individual ESCC cases.As a result,we successfully constructed an OS-related genes(OSRGs)model and found that the survival rate of high-risk groups was lower than that of low-risk groups.The AUC of the ROC verified the strong prediction performance of the signal in these two cohorts further.According to independent prognostic analysis,the RS was identified as an independent risk factor for ESCC.The nomogram and follow-up data revealed that the RS possesses favorable predictive value for the prognosis of ESCC patients.qRT-PCR detection demonstrated increased expression of MPC1,COX6C,CYB5R3,CASP7,and CYCS in esophageal cancer patients.In conclusion,we have constructed an OSRGs model for ESCC to predict patients’prognosis,offering a novel insight into the potential application of the OSRGs model in ESCC.
基金supported by National Natural Science Foundation of China (No. 31902287)Key R&D and Promotion Projects of Henan Province (No. 242102310467, No. 242102310240 and No. 23210 2310132)Henan Department of Public Health (No. LHGJ20221021)。
文摘Hepatocellular carcinoma(HCC) is considered the fifth most prevalent cancer among all types of cancers and has the third most morbidity value. It has the most frequent duplication time and a high recurrence rate. Recently, the most unique technique used is liquid biopsies, which carry many markers;the most prominent is circulating tumor DNA(ctDNA). Varied methods are used to investigate ctDNA, including various forms of polymerase chain reaction(PCR) [emulsion PCR(ePCR), digital PCR(dPCR), and bead, emulsion, amplification, magnetic(BEAMing) PCR]. Hence ctDNA is being recognized as a potential biomarker that permits early cancer detection,treatment monitoring, and predictive data on tumor burden are subjective to therapy or surgery. Numerous ctDNA biomarkers have been investigated based on their alterations such as 1) single nucleotide variations(either insertion or deletion of a nucleotide) markers including TP53, KRAS, and CCND1;2) copy number variations which include markers such as CDK6, EFGR, MYC and BRAF;3) DNA methylation(RASSF1A, SEPT9, KMT2C and CCNA2);4) homozygous mutation includes ctDNA markers as CDKN2A, AXIN1;and 5) gain or loss of function of the genes, particularly for HCC. Various researchers have conducted many studies and gotten fruitful results.Still, there are some drawbacks to ctDNA namely low quantity, fragment heterogeneity, less stability, limited mutant copies and standards, and differential sensitivity. However, plenty of investigations demonstrate ctDNA's significance as a polyvalent biomarker for cancer and can be viewed as a future diagnostic, prognostic and therapeutic agent. This article overviews many conditions in genetic changes linked to the onset and development of HCC, such as dysregulated signaling pathways, somatic mutations, single-nucleotide polymorphisms, and genomic instability. Additionally, efforts are also made to develop treatments for HCC that are molecularly targeted and to unravel some of the genetic pathways that facilitate its early identification.
基金the National Natural Science Foundation of China,No.8236110677Central to guide local scientific and Technological Development,No.ZYYDDFFZZJ-1+1 种基金Natural Science Foundation of Gansu Province,China,No.18JR2RA033Gansu Da Vinci Robot High-End Diagnosis and Treatment Team Construction Project,National Key Research and Development Program,No.2020RCXM076.
文摘BACKGROUND Gastric cancer has a high incidence and fatality rate,and surgery is the preferred course of treatment.Nonetheless,patient survival rates are still low,and the incidence of major postoperative complications cannot be disregarded.The systemic inflammatory response,nutritional level,and coagulation status are key factors affecting the postoperative recovery and prognosis of gastric cancer patients.The systemic inflammatory response index(SIRI)and the albumin fibrinogen ratio(AFR)are two valuable comprehensive indicators of the severity and prognosis of systemic inflammation in various medical conditions.AIM To assess the clinical importance and prognostic significance of the SIRI scores and the AFR on early postoperative outcomes in patients undergoing radical gastric cancer surgery.METHODS We conducted a retrospective analysis of the clinicopathological characteristics and relevant laboratory indices of 568 gastric cancer patients from January 2018 to December 2019.We calculated and compared two indicators of inflammation and then examined the diagnostic ability of combined SIRI and AFR values for serious early postoperative complications.We scored the patients and categorized them into three groups based on their SIRI and AFR levels.COX analysis was used to compare the three groups of patients the prognostic value of various preoperative SIRI-AFR scores for 5-year overall survival(OS)and disease-free survival(DFS).RESULTS SIRI-AFR scores were an independent risk factor for prognosis[OS:P=0.004;hazards ratio(HR)=3.134;DFS:P<0.001;HR=3.543]and had the highest diagnostic power(area under the curve:0.779;95%confidence interval:0.737-0.820)for early serious complications in patients with gastric cancer.The tumor-node-metastasis stage(P=0.001),perioperative transfusion(P=0.044),positive carcinoembryonic antigen(P=0.014)findings,and major postoperative complications(P=0.011)were factors associated with prognosis.CONCLUSION Preoperative SIRI and AFR values were significantly associated with early postoperative survival and the occurrence of severe complications in gastric cancer patients.
文摘BACKGROUND Gastric cancer(GC)is a highly aggressive malignancy with a heterogeneous nature,which makes prognosis prediction and treatment determination difficult.Inflammation is now recognized as one of the hallmarks of cancer and plays an important role in the aetiology and continued growth of tumours.Inflammation also affects the prognosis of GC patients.Recent reports suggest that a number of inflammatory-related biomarkers are useful for predicting tumour prognosis.However,the importance of inflammatory-related biomarkers in predicting the prognosis of GC patients is still unclear.AIM To investigate inflammatory-related biomarkers in predicting the prognosis of GC patients.was constructed using the least absolute shrinkage and selection operator Cox regression model based on the GEO database.GC patients from the GSE26253 cohort were used for validation.Univariate and multivariate Cox analyses were used to determine the independent prognostic factors,and a prognostic nomogram was established.The calibration curve and the area under the curve based on receiver operating characteristic analysis were utilized to evaluate the predictive value of the nomogram.The decision curve analysis results were plotted to quantify and assess the clinical value of the nomogram.Gene set enrichment analysis was performed to explore the potential regulatory pathways involved.The relationship between tumour immune infiltration status and risk score was analysed via Tumour Immune Estimation Resource and CIBERSORT.Finally,we analysed the association between risk score and patient sensitivity to commonly used chemotherapy and targeted therapy agents.RESULTS A prognostic model consisting of three inflammatory-related genes(MRPS17,GUF1,and PDK4)was constructed.Independent prognostic analysis revealed that the risk score was a separate prognostic factor in GC patients.According to the risk score,GC patients were stratified into high-and low-risk groups,and patients in the high-risk group had significantly worse prognoses according to age,sex,TNM stage and Lauren type.Consensus clustering identified three subtypes of inflammation that could predict GC prognosis more accurately than traditional grading and staging.Finally,the study revealed that patients in the low-risk group were more sensitive to certain drugs than were those in the high-risk group,indicating a link between inflammation-related genes and drug sensitivity.CONCLUSION In conclusion,we established a novel three-gene prognostic signature that may be useful for predicting the prognosis and personalizing treatment decisions of GC patients.
文摘Introduction: Retroplacental haematoma (RPH) is a very serious complication of pregnancy, with life-threatening consequences for both the mother and foetus. The aim of this study is to determine the incidence and epidemiological characteristics of patients with retroplacental haematoma (RPH) and describe the maternal-foetal complications at Bouaké University Hospital. Methods: This was a cross-sectional prospective, descriptive and analytical study carried out at Bouaké University Hospital over a period of 3 years, from January 1, 2019 to December 31, 2021. All parturients with RPH whose delivery took place at the hospital were included in the study. Data were entered and analysed using EPI INFO software version 7.2.2.6. Results: We recorded 2,0959 deliveries, including 202 cases of RPH, representing an incidence of 0.96%. The 21 to 35 age group accounted for 64.4%, multigestas and large multigestas accounted for 58.5% and multiparas accounted for 41.6%. The main signs on clinical examination were metrorrhagia (100%), arterial hypertension (84.6%) and cervical cerclage (79.7%). Preeclampsia accounted for 50% of per-gestational pathologies. Maternal mortality was 12.9%. Morbidity was dominated by anaemia in 64.1%, followed by disseminated intravascular coagulation (DIC) in 21.8%, and the factors associated with this maternal prognosis were multiple gestations, multiparity, Sher grade IIIb and the occurrence of complications such as DIC, shock, renal complications and HELLP syndrome. Neonatal mortality was 79.2%, and the factors associated with these fetal prognoses were cup size ≥ 5 cm and hematoma weight ≥ 500 g. Conclusion: Better screening of at-risk populations, early diagnosis and treatment in an organised and equipped medical and surgical facility would improve prognosis.
文摘BACKGROUND Heat shock proteins(HSPs)are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overex-pressed in many cancers.The prognostic significance of HSPs and their regulatory factors,such as heat shock factor 1(HSF1)and CHIP,are poorly understood.AIM To investigate the relationship between HSP expression and prognosis in esophageal and esophagogastric cancer.METHODS A systematic review was conducted in accordance with PRISMA recommend-ations(PROSPERO:CRD42022370653),on Embase,PubMed,Cochrane,and LILACS.Cohort,case-control,and cross-sectional studies of patients with eso-phagus or esophagogastric cancer were included.HSP-positive patients were compared with HSP-negative,and the endpoints analyzed were lymph node metastasis,tumor depth,distant metastasis,and overall survival(OS).HSPs were stratified according to the HSP family,and the summary risk difference(RD)was calculated using a random-effect model.RESULTS The final selection comprised 27 studies,including esophageal squamous cell carcinoma(21),esophagogastric adenocarcinoma(5),and mixed neoplasms(1).The pooled sample size was 3465 patients.HSP40 and 60 were associated with a higher 3-year OS[HSP40:RD=0.22;95%confidence interval(CI):0.09-0.35;HSP60:RD=0.33;95%CI:0.17-0.50],while HSF1 was associated with a poor 3-year OS(RD=-0.22;95%CI:-0.32 to-0.12).The other HSP families were not associated with long-term survival.HSF1 was associated with a higher probability of lymph node metastasis(RD=-0.16;95%CI:-0.29 to-0.04).HSP40 was associated with a lower probability of lymph node dissemination(RD=0.18;95%CI:0.03-0.33).The expression of other HSP families was not significantly related to tumor depth and lymph node or distant metastasis.CONCLUSION The expression levels of certain families of HSP,such as HSP40 and 60 and HSF1,are associated with long-term survival and lymph node dissemination in patients with esophageal and esophagogastric cancer.
基金Supported by National Natural Science Foundation of China,No.82072736 and No.81874184the Key Project of Hubei Health Commission,No.WJ2019Q030.
文摘BACKGROUND There is currently a shortage of accurate,efficient,and precise predictive instruments for rectal neuroendocrine neoplasms(NENs).AIM To develop a predictive model for individuals with rectal NENs(R-NENs)using data from a large cohort.METHODS Data from patients with primary R-NENs were retrospectively collected from 17 large-scale referral medical centers in China.Random forest and Cox proportional hazard models were used to identify the risk factors for overall survival and progression-free survival,and two nomograms were constructed.RESULTS A total of 1408 patients with R-NENs were included.Tumor grade,T stage,tumor size,age,and a prognostic nutritional index were important risk factors for prognosis.The GATIS score was calculated based on these five indicators.For overall survival prediction,the respective C-indexes in the training set were 0.915(95%confidence interval:0.866-0.964)for overall survival prediction and 0.908(95%confidence interval:0.872-0.944)for progression-free survival prediction.According to decision curve analysis,net benefit of the GATIS score was higher than that of a single factor.The time-dependent area under the receiver operating characteristic curve showed that the predictive power of the GATIS score was higher than that of the TNM stage and pathological grade at all time periods.CONCLUSION The GATIS score had a good predictive effect on the prognosis of patients with R-NENs,with efficacy superior to that of the World Health Organization grade and TNM stage.
文摘BACKGROUND Gastric cancer(GC)has a high mortality rate worldwide.Despite significant progress in GC diagnosis and treatment,the prognosis for affected patients still remains unfavorable.AIM To identify important candidate genes related to the development of GC and iden-tify potential pathogenic mechanisms through comprehensive bioinformatics analysis.METHODS The Gene Expression Omnibus database was used to obtain the GSE183136 dataset,which includes a total of 135 GC samples.The limma package in R software was employed to identify differentially expressed genes(DEGs).Thereafter,enrichment analyses of Gene Ontology(GO)terms and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways were performed for the gene modules using the clusterProfile package in R software.The protein-protein interaction(PPI)networks of target genes were constructed using STRING and visualized by Cytoscape software.The common hub genes that emerged in the cohort of DEGs that was retrieved from the GEPIA database were then screened using a Venn Diagram.The expression levels of these overlapping genes in stomach adenocarcinoma samples and non-tumor samples and their association with prognosis in GC patients were also obtained from the GEPIA database and Kaplan-Meier curves.Moreover,real-time quantitative polymerase chain reaction(RT-qPCR)and western blotting were performed to determine the mRNA and protein levels of glutamic-pyruvic transaminase(GPT)in GC and normal immortalized cell lines.In addition,cell viability,cell cycle distribution,migration and invasion were evaluated by cell counting kit-8,flow cytometry and transwell assays.Furthermore,we also conducted a retrospective analysis on 70 GC patients diagnosed and surgically treated in Wenzhou Central Hospital,Dingli Clinical College of Wenzhou Medical University,The Second Affiliated Hospital of Shanghai University between January 2017 to December 2020.The tumor and adjacent normal samples were collected from the patients to determine the potential association between the expression level of GPT and the clinical as well as pathological features of GC patients.RESULTS We selected 19214 genes from the GSE183136 dataset,among which there were 250 downregulated genes and 401 upregulated genes in the tumor samples of stage III-IV in comparison to those in tumor samples of stage I-II with a P-value<0.05.In addition,GO and KEGG results revealed that the various upregulated DEGs were mainly enriched in plasma membrane and neuroactive ligand-receptor interaction,whereas the downregulated DEGs were primarily enriched in cytosol and pancreatic secretion,vascular smooth muscle contraction and biosynthesis of the different cofactors.Furthermore,PPI networks were constructed based on the various upregulated and downregulated genes,and there were a total 15 upregulated and 10 downregulated hub genes.After a comprehensive analysis,several hub genes,including runt-related transcription factor 2(RUNX2),salmonella pathogenicity island 1(SPI1),lysyl oxidase(LOX),fibrillin 1(FBN1)and GPT,displayed prognostic values.Interestingly,it was observed that GPT was downregulated in GC cells and its upregulation could suppress the malignant phenotypes of GC cells.Furthermore,the expression level of GPT was found to be associated with age,lymph node metastasis,pathological staging and distant metastasis(P<0.05).CONCLUSION RUNX2,SPI1,LOX,FBN1 and GPT were identified key hub genes in GC by bioinformatics analysis.GPT was significantly associated with the prognosis of GC,and its upregulation can effectively inhibit the proliferative,migrative and invasive capabilities of GC cells.
基金Supported by Scientific and Technological Project of Henan Province,No.212102210140.
文摘BACKGROUND Liver cancer is one of the deadliest malignant tumors worldwide.Immunotherapy has provided hope to patients with advanced liver cancer,but only a small fraction of patients benefit from this treatment due to individual differences.Identifying immune-related gene signatures in liver cancer patients not only aids physicians in cancer diagnosis but also offers personalized treatment strategies,thereby improving patient survival rates.Although several methods have been developed to predict the prognosis and immunotherapeutic efficacy in patients with liver cancer,the impact of cell-cell interactions in the tumor microenvir-onment has not been adequately considered.AIM To identify immune-related gene signals for predicting liver cancer prognosis and immunotherapy efficacy.METHODS Cell grouping and cell-cell communication analysis were performed on single-cell RNA-sequencing data to identify highly active cell groups in immune-related pathways.Highly active immune cells were identified by intersecting the highly active cell groups with B cells and T cells.The significantly differentially expressed genes between highly active immune cells and other cells were subsequently selected as features,and a least absolute shrinkage and selection operator(LASSO)regression model was constructed to screen for diagnostic-related features.Fourteen genes that were selected more than 5 times in 10 LASSO regression experiments were included in a multivariable Cox regression model.Finally,3 genes(stathmin 1,cofilin 1,and C-C chemokine ligand 5)significantly associated with survival were identified and used to construct an immune-related gene signature.RESULTS The immune-related gene signature composed of stathmin 1,cofilin 1,and C-C chemokine ligand 5 was identified through cell-cell communication.The effectiveness of the identified gene signature was validated based on experi-mental results of predictive immunotherapy response,tumor mutation burden analysis,immune cell infiltration analysis,survival analysis,and expression analysis.CONCLUSION The findings suggest that the identified gene signature may contribute to a deeper understanding of the activity patterns of immune cells in the liver tumor microenvironment,providing insights for personalized treatment strategies.