Gallbladder carcinosarcoma with a poor prognosis: A case report

BACKGROUND Carcinosarcoma of the gallbladder is a rare malignant tumor with a very poor prognosis.To date,only approximately 100 patients have been reported in the English literature.The prognosis of this tumor type is poor,the preoperative diagnosis is difficult,and there is a possibility of a misdiagnosis.We present an unsuccessful case of carcinosarcoma of the gallbladder with a preoperative misdiagnosis and rapid early postoperative recurrence.Therefore,we have a deeper understanding of the poor prognosis of gallbladder carcinosarcoma(GBC)patients.CASE SUMMARY The patient is a 65-year-old male.He was admitted to the hospital because of right upper abdomen distending pain and discomfort for half a month.Abdominal magnetic resonance imaging revealed a polycystic mass in the right lobe of the liver and the fossa of the gallbladder.After admission,the patient was diagnosed with a liver abscess,which was treated by abscess puncture drainage.Obviously,this treatment was unsuccessful.Hepatectomy and cholecystectomy were performed one month after the puncture.Postoperative pathologic examination revealed carcinosarcoma of the gallbladder,and the resected specimen contained two tumor components.One month after surgery,the patient's tumor recurred in situ and started to compress the duodenum,resulting in duodenal obstruction and bleeding.The treatment was not effective.The patient died of gastrointestinal hemorrhage and hypovolemic shock.CONCLUSION Carcinosarcoma of the gallbladder is a rare malignant tumor that is easily misdiagnosed preoperatively and has a poor prognosis.

Autosomal Dominant Polycystic Kidney Disease: Epidemiological, Clinical Aspects and Predictive Factors of Poor Renal Prognosis (About 300 Cases)

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is a common, multisystemic, and progressive hereditary disease. It accounts for 6 to 8% of incident cases of end-stage chronic renal disease (ESRD) in developed countries. The aim of this study is to describe the predictive factors for the development of end-stage chronic kidney disease (CKD) in the course of this disease. Material and Methods: This is a retrospective, descriptive, and analytical study including 300 cases of ADPKD collected at the Nephrology Department of Ibn-Sina Hospital in Rabat over a period of 30 years (1993 to 2023). Included in the study are all patients with ADPKD meeting the ultrasound diagnostic criteria. The analysis focused on demographic, clinical, paraclinical, evolutionary data, as well as prognostic factors associated with renal function deterioration. Results: The mean age of patients at diagnosis is 51.53 +/− 17 years [16 - 93] with a male predominance. The median serum creatinine at diagnosis is 15.5 mg/l [10 - 34]. 21% of patients had ESRD (eGFR 300 mg/24h (21%). The most common cystic complication is hemorrhage (12.3%). 21.3% of patients had hepatorenal polycystic disease. In adjusted analysis, the predictive risk factors for the occurrence of ESRD were smoking (p = 0.019), anemia (p Conclusion: ADPKD can progress insidiously to ESRD. Identification and early treatment of predictive factors for poor renal prognosis could contribute to a better outcome for this disease.

Systematic review of risk factors,prognosis,and management of colorectal signet-ring cell carcinoma

BACKGROUND Colorectal signet-ring cell carcinoma(CSRCC)is a rare clinical entity which accounts for approximately 1%of all colorectal cancers.Although multiple studies concerning this specific topic have been published in the past decades,the pathogenesis,associated risk factors,and potential implications on treatment are still poorly understood.Besides the low incidence,historically confusing histological criteria have resulted in confusing data.Nevertheless,the rising incidence of CSRCC along with relatively young age at presentation and associated dismal prognosis,highlight the actual interest to synthesize the known literature regarding CSRCC.AIM To provide an updated overview of risk factors,prognosis,and management of CSRCC.METHODS A literature search in the MEDLINE/PubMed database was conducted with the following search terms used:‘Signet ring cell carcinoma’and‘colorectal’.Studies in English language,published after January 1980,were included.Studies included in the qualitative synthesis were evaluated for content concerning epidemiology,risk factors,and clinical,diagnostic,histological,and molecular features,as well as metastatic pattern and therapeutic management.If possible,presented data was extracted in order to present a more detailed overview of the literature.RESULTS In total,67 articles were included for qualitative analysis,of which 54 were eligible for detailed data extraction.CSRCC has a reported incidence between 0.1%-2.4%and frequently presents with advanced disease stage at the time of diagnosis.CSRCC is associated with an impaired overall survival(5-year OS:0%-46%)and a worse stagecorrected outcome compared to mucinous and not otherwise specified adenocarcinoma.The systematic use of exploratory laparoscopy to determine the presence of peritoneal metastases has been advised.Surgery is the mainstay of treatment,although the rates of curative resection in CSRCC(21%-82%)are lower compared to those in other histological types.In case of peritoneal metastasis,cytoreductive surgery with hyperthermic intraperitoneal chemotherapy should only be proposed in selected patients.CONCLUSION CSRCC is a rare clinical entity most often characterized by young age and advanced disease at presentation.As such,diagnostic modalities and therapeutic approach should be tailored accordingly.

Relationship between body mass index and short-term postoperative prognosis in patients undergoing colorectal cancer surgery

BACKGROUND Obesity is a state in which excess heat is converted into excess fat,which accumulates in the body and may cause damage to multiple organs of the circulatory,endocrine,and digestive systems.Studies have shown that the accumulation of abdominal fat and mesenteric fat hypertrophy in patients with obesity makes laparoscopic surgery highly difficult,which is not conducive to operation and affects patient prognosis.However,there is still controversy regarding these conclusions.AIM To explore the relationship between body mass index(BMI)and short-term prognosis after surgery for colorectal cancer.METHODS PubMed,Embase,Ovid,Web of Science,CNKI,and China Biology Medicine Disc databases were searched to obtain relevant articles on this topic.After the articles were screened according to the inclusion and exclusion criteria and the risk of literature bias was assessed using the Newcastle-Ottawa Scale,the prognostic indicators were combined and analyzed.RESULTS A total of 16 articles were included for quantitative analysis,and 15588 patients undergoing colorectal cancer surgery were included in the study,including 3775 patients with obesity and 11813 patients without obesity.Among them,12 articles used BMI≥30 kg/m^(2)and 4 articles used BMI≥25 kg/m^(2)for the definition of obesity.Four patients underwent robotic colorectal surgery,whereas 12 underwent conventional laparoscopic colorectal resection.The quality of the literature was good.Meta-combined analysis showed that the overall complication rate of patients with obesity after surgery was higher than that of patients without obesity[OR=1.35,95%CI:1.23-1.48,Z=6.25,P<0.0001].The incidence of anastomotic leak after surgery in patients with obesity was not significantly different from that in patients without obesity[OR=0.99,95%CI:0.70-1.41),Z=-0.06,P=0.956].The incidence of surgical site infection(SSI)after surgery in patients with obesity was higher than that in patients without obesity[OR=1.43,95%CI:1.16-1.78,Z=3.31,P<0.001].The incidence of reoperation in patients with obesity after surgery was higher than that in patients without obesity;however,the difference was not statistically significant[OR=1.15,95%CI:0.92-1.45,Z=1.23,P=0.23];Patients with obesity had lower mortality after surgery than patients without obesity;however,the difference was not statistically significant[OR=0.61,95%CI:0.35-1.06,Z=-1.75,P=0.08].Subgroup analysis revealed that the geographical location of the institute was one of the sources of heterogeneity.Robot-assisted surgery was not significantly different from traditional laparoscopic resection in terms of the incidence of complications.CONCLUSION Obesity increases the overall complication and SSI rates of patients undergoing colorectal cancer surgery but has no influence on the incidence of anastomotic leak,reoperation rate,and short-term mortality rate.

Relationship between preoperative psychological stress and shortterm prognosis in elderly patients with femoral neck fracture

BACKGROUND Older adults are at high risk of femoral neck fractures(FNFs).Elderly patients face and adapt to significant psychological burdens,resulting in different degrees of psychological stress response.Total hip replacement is the preferred treatment for FNF in elderly patients;however,some patients have poor postoperative prognoses,and the underlying mechanism is unknown.We speculated that the postoperative prognosis of elderly patients with FNF may be related to preoperative psychological stress.AIM To explore the relationship between preoperative psychological stress and the short-term prognosis of elderly patients with FNF.METHODS In this retrospective analysis,the baseline data,preoperative 90-item Symptom Checklist score,and Harris score within 6 months of surgery of 120 elderly patients with FNF who underwent total hip arthroplasty were collected.We analyzed the indicators of poor short-term postoperative prognosis and the ability of the indicators to predict poor prognosis and compared the correlation between the indicators and the Harris score.RESULTS Anxiety,depression,garden classification of FNF,cause of fracture,FNF reduction quality,and length of hospital stay were independent influencing factors for poor short-term postoperative prognoses in elderly patients with FNF(P<0.05).The areas under the curve for anxiety,depression,and length of hospital stay were 0.742,0.854,and 0.749,respectively.The sensitivities of anxiety,depression,garden classification of FNF,and prediction of the cause of fracture were 0.857,0.786,0.821,and 0.821,respectively.The specificities of depression,FNF quality reduction,and length of hospital stay were the highest at 0.880,0.783,and 0.761,respectively.Anxiety,depression,and somatization scores correlated moderately with Harris scores(r=-0.523,-0.625,and-0.554;all P<0.001).CONCLUSION Preoperative anxiety,depression,and somatization are correlated with poor short-term prognosis in elderly patients with FNF and warrant consideration.

Oncogenic ADAM28 induces gemcitabine resistance and predicts a poor prognosis in pancreatic cancer

BACKGROUND Pancreatic cancer is a major cause of cancer-related death,with a 5-year overall survival rate being below 5%.The main causes of poor prognosis in pancreatic cancer include easy metastasis,high recurrence rate,and robust drug resistance.Gemcitabine is a first-line drug for patients with unresectable pancreatic cancer.However,due to drug resistance,the clinical effect is not satisfactory.ADAM28 is reported as a tumor promoter in some cancers,but its role in pancreatic cancer and gemcitabine chemoresistance in pancreatic cancer has not been elucidated.AIM To identify if ADAM28 can act as an important target to reverse the gemcitabine drug resistance in pancreatic cancer.METHODS RNA-sequence analysis was applied to explore the potential targets involved in the gemcitabine of pancreatic cancer.SW1990 pancreatic cancer cells were treated with an increased dose of gemcitabine,and the mRNA levels of ADAM28 were evaluated by RT-PCR.The protein and mRNA levels of ADAM28 were confirmed in the gemcitabine resistant and parallel SW1990 cells.The ADAM28 expression was also assessed in TCGA and GEO databases,and the results were confirmed in the collected tumor and adjacent normal tissues.The overall survival(OS)rate and relapse-free survival(RFS)rate of pancreatic cancer patients with high ADAM28 level and low ADAM28 level in TCGA were evaluated with Kaplan-Meier Plotter.Furthermore,the OS rate was calculated in pancreatic cancer patients with high tumor mutation burden(TMB)and low TMB.CCK-8 assay was used to examine the effect of ADAM28 on the viability of SW1990 cells.The ADAM28 and its co-expressed genes were analyzed in the cBioPortal for cancer genomics and subjected to GSEA pathway analysis.The correlations of ADAM28 with GSTP1,ABCC1,GSTM4,and BCL2 were analyzed based on TCGA data on pancreatic cancer.RESULTS RNA-sequence analysis identified that ADAM28 was overexpressed in gemcitabine-resistant cells,and gemcitabine treatment could induce the expression of ADAM28.The mRNA and protein levels of ADAM28 were elevated in gemcitabine-resistant SW1990 cells compared with parallel cells.Also,the expression of ADAM28 was upregulated in pancreatic tumor tissues against normal pancreatic tissues.Notably,ADAM28 was highly expressed in the classical type than in the basal tumor type.Furthermore,the high expression of ADAM28 was associated with low OS and RFS rates.Interestingly,the high levels of ADAM28 was associated with a significantly lower OS rate in the high TMB patients,but not in the low TMB patients.Moreover,overexpression of ADAM28 could reduce the cell viability inhibition by gemcitabine,and knockdown of ADAM28 could enhance the proliferation inhibition by gemcitabine.The GSEA analysis showed that ADAM28 was related to the regulation of drug metabolism,and ADAM28 was significantly positively correlated with GSTP1,ABCC1,GSTM4,and BCL2.CONCLUSION This study demonstrates that ADAM28 is overexpressed in pancreatic cancer,and closely involved in the regulation of gemcitabine resistance.Overexpression of ADAM28 is a novel prognostic biomarker in pancreatic cancer.

CCL7 and CCL21 overexpression in gastric cancer is associated with lymph node metastasis and poor prognosis

AIM： To investigate how a complex network of CC chemokine ligands （eeLs） and their receptors influence the progression of tumor and metastasis.METHODS： In the present study, we used immunohistochemistry to examine the expression of CCL7, CCL8 and CCL21 in 194 gastric cancer samples and adjacent normal tissues. We analyzed their correlation with tumor metastasis, clinicopathologic parameters and clinical outcome.RESULTS： We found that the higher expression of CCL7 and CCL21 in cancer tissues than in normal tissues was significantly correlated with advanced depth of wall invasion, lymph node metastasis and higher tumornode metastasis stage. Moreover, Kaplan-Meier survival analysis revealed that CCL7 and CCL21 overexpression in cancer tissues was correlated with poor prognosis.CONCLUSION： These results suggest that overexpression of these two CC chemokine ligands is associ- ated with tumor metastasis and serves as a prognostic factor in patients with gastric cancer.

Neuron-glial antigen 2 overexpression in hepatocellular carcinoma predicts poor prognosis

AIM:To investigate whether neuron-glial antigen 2(NG2) could be an effective prognostic marker in hepatocellular carcinoma(HCC).METHODS:NG2 expression was semi-quantitatively scored from the immunohistochemistry(IHC) data based on the number of positive cells and the staining intensity.A total of 132 HCC specimens and 96 adjacent noncancerous tissue samples were analyzed by IHC for NG2 protein expression.To confirm the NG2 expression levels observed by IHC,we measured NG2 expression in 30 randomly selected tumor and adjacent noncancerous tissue samples by quantitative real-time polymerase chain reaction and Western blot.The correlations between NG2 protein expression and the clinicopathological features of HCC patients were analyzed using the χ2 test.To assess the prognostic value of NG2 for HCC,the association between NG2 expression and survival was analyzed using the KaplanMeier method with the log-rank test.To further evaluate the prognostic value of NG2 expression,a Cox multivariate proportional hazards regression analysis was performed with all the variables to derive risk estimates related to disease-free and overall survival and to control for confounders.RESULTS:High NG2 expression was observed in significantly more primary tumor samples(63.6%; 84/132) compared with the adjacent noncancerous tissue samples(28.1%; 27/96)(P < 0.0001).Moreover,high NG2 protein expression was closely associated with tumor differentiation(χ2 = 9.436,P = 0.0089),recurrence(χ2 = 5.769,P = 0.0163),tumor-nodemetastasis(TNM) stage(χ2 = 8.976,P = 0.0027),and invasion(χ2 = 5.476,P = 0.0193).However,no significant relationship was observed between NG2 protein expression in HCC and other parameters,such as age,sex,tumor size,serum alpha fetoprotein(AFP),tumor number,or tumor capsule.The log-rank test indicated a significant difference in the overall survival of HCC patients with high NG2 expression compared with those with low NG2 expression(29.2% vs 9.5%,P < 0.001).Moreover,NG2 expression in HCC tissue significantly correlated with disease-free survival(15.2% vs 6.7%,P < 0.001).Multivariate analysis showed that NG2 expression(HR = 2.035,P = 0.002),serum AFP(HR = 1.903,P = 0.003),TNM stage(HR = 2.039,P = 0.001),and portal vein invasion(HR = 1.938,P = 0.002) were independent prognostic indicators for OS in HCC patients.Furthermore,NG2 expression(HR = 1.974,P = 0.003),serum AFP(HR = 1.767,P = 0.008),TNM stage(HR = 2.078,P = 0.001),tumor capsule(HR = 0.652,P = 0.045),and portal vein invasion(HR = 1.941,P = 0.002) were independent prognostic indicators for DFS in HCC patients.CONCLUSION:The up-regulation of NG2 is associated with poor prognosis in HCC.Therefore,NG2 could be useful as an additional prognostic marker to increase the resolution of traditional approaches.

Clinicopathological characteristics and prognosis of 232 patients with poorly differentiated gastric neuroendocrine neoplasms

BACKGROUND Poorly differentiated gastric neuroendocrine neoplasms(PDGNENs)include gastric neuroendocrine carcinoma(NEC)and mixed adenoneuroendocrine carcinoma,which are highly malignant and rare tumors,and their incidence has increased over the past few decades.However,the clinicopathological features and outcomes of patients with PDGNENs have not been completely elucidated.AIM To investigate the clinicopathological characteristics and prognostic factors of patients with PDGNENs.METHODS The data from seven centers in China from March 2007 to November 2019 were analyzed retrospectively.RESULTS Among the 232 patients with PDGNENs,191(82.3%)were male,with an average age of 62.83±9.11 years.One hundred and thirteen(49.34%)of 229 patients had a stage III disease and 86(37.55%)had stage IV disease.Three(1.58%)of 190 patients had no clinical symptoms,while 187(98.42%)patients presented clinical symptoms.The tumors were mainly(89.17%)solitary and located in the upper third of the stomach(cardia and fundus of stomach:115/215,53.49%).Most lesions were ulcers(157/232,67.67%),with an average diameter of 4.66±2.77 cm.In terms of tumor invasion,the majority of tumors invaded the serosa(116/198,58.58%).The median survival time of the 232 patients was 13.50 mo(7,31 mo),and the overall 1-year,3-year,and 5-year survival rates were 49%,19%,and 5%,respectively.According to univariate analysis,tumor number,tumor diameter,gastric invasion status,American Joint Committee on Cancer(AJCC)stage,and distant metastasis status were prognostic factors for patients with PDGNENs.Multivariate analysis showed that tumor number,tumor diameter,AJCC stage,and distant metastasis status were independent prognostic factors for patients with PDGNENs.CONCLUSION The overall prognosis of patients with PDGNENs is poor.The outcomes of patients with a tumor diameter>5 cm,multiple tumors,and stage IV tumors are worse than those of other patients.

Expression of sialyl Lewis^a relates to poor prognosis in cholangiocarcinoma

AIM: High levels of serum sialyl Lewisa (sLea) are frequently found in cholangiocarcinoma (CCA) patients and have been suggested to be a serum marker for CCA. However, the significance of this antigen in CCA is unknown. In this study, the clinical significance of sLea expression in CCA tissues and the possible role of sLea in vascular invasion in vitro were elucidated. METHODS: Expression of sLea in tumor tissues of 77 patients with mass-forming CCA and 33 with periductal infiltrating CCA was determined using immunohistochemistry. The in vitro assays on adhesion and transmigration of CCA cells to human umbilical vein endothelial cells were compared between CCA cell lines with and without sLea expression. RESULTS: sLea was aberrantly expressed in 60% of CCA tumor tissues. A significant relationship was found between the frequency of sLea expression and the mass-forming type CCA (P= 0.041), well differentiated histological grading (P=0.029), and vascular invasion (P=0.030). Patients with positive sLea expression had a significantly poorer prognosis (21.28 wk, 95% CI=16.75-25.81 wk) than those negative for sLea (37.30 wk, 95% CI=27.03-47.57 wk) (P<0.001). Multivariate analysis with adjustment for all covariates showed that patients positive for sLea possessed a 2.3-fold higher risk of death than patients negative for sLea (P<0.001). The role of sLea in vascular invasion was demonstrated using in vitro adhesion and transmigration assays. KKU-M213, a human CCA cell-line with a high expression of sLea, adhered and transmigrated to IL-1β-activated endothelial cells of the human umbilical vein more than KKU-100, the line without sLea expression (P<0.001). These processes were significantly diminished when the antibodies specific to either sLea or E-selectin were added to the assays (P<0.001) CONCLUSION: This study demonstrates the clinical significance of sLea expression in vascular invasion, and an unfavorable outcome in CCA. The role of sLea in vascular invasion which may lead to poor prognosis is supported by the in vitro adhesion and transmigration studies.

Myofibrillogenesis regulator-1 overexpression is associated with poor prognosis of gastric cancer patients

AIM: To investigate the expression of myofibrillogenesis regulator-1 (MR-1) in relation to clinicopathological parameters and postoperative survival in a group of Chinese patients with gastric cancer. METHODS: In our previous study of human wholegenome gene expression profiling, the differentially expressed genes were detected in the gastric cancer and its adjacent noncancerous mucosa. We found that MR-1 was associated with the location and differentiation of tumors. In this study, MR-1 protein expression was determined by immunohistochemistry in specimens of primary cancer and the adjacent noncancerous tissues from gastric cancer patients. A set of real-time quantitative polymerase chain reaction assays based on the Universal ProbeLibrary-a collection of 165 presynthesized, fluorescence-labeled locked nucleic acid hydrolysis probes-was designed specifically to detect the expression of MR-1 mRNA. The correlation was analyzed between the expression of MR-1 and other tumor characteristics which may influence the prognosis of gastric cancer patients. A retrospective cohort study on the prognosis was carried out and clinical data were collected from medical records. RESULTS: MR-1 mRNA and protein could be detected in gastric cancer tissues as well as in matched noncancerous tissues. MR-1 was up-regulated at both mRNA (5.459 ± 0.639 vs 1.233 ± 0.238, P < 0.001) and protein levels (34.2% vs 13.2%, P = 0.003) in gastric cancer tissues. Correlation analysis demonstrated that high expression of MR-1 in gastric cancer was significantly correlated with clinical stage (P = 0.034). Kaplan-Meier analysis showed that the postoperative survival of the MR-1 positive group tended to be poorer than that of the MR-1 negative group, and the difference was statistically significant (P = 0.002). Among all the patients with stageⅠ-Ⅳ carcinoma, the 5-year survival rates of MR-1 positive and negative groups were 50.40% and 12.70%, respectively, with respective median survival times of 64.27 mo (95%CI: 13.41-115.13) and 16.77 mo (95%CI: 8.80-24.74). Univariate and multivariate analyses were performed to compare the impact of MR-1 expression and other clinicopathological parameters on prognosis. In a univariate analysis on all 70 specimens, 6 factors were found to be significantly associated with the overall survival statistically: including MR-1 expression, depth of invasion, distant metastasis, lymph node metastasis, vascular invasion and the tumor node metastasis (TNM) stage based on the 7th edition of the International Union against Cancer TNM classification. To avoid the influence caused by univariate analysis, the expressions of MR-1 as well as other parameters were examined in multivariate Cox analysis. Clinicopathological variables that might affect the prognosis of gastric cancer patients were analyzed by Cox regression analysis, which showed that MR-1 expression and TNM stage were independent predictors of postoperative survival. The best mathematical multivariate Cox regression model consisted of two factors: MR-1 expression and TNM stage. Our results indicated that MR-1 protein could act as an independent marker for patient overall survival [Hazard ratio (HR): 2.215, P = 0.043]. CONCLUSION: MR-1 is an important variable that can be used to evaluate the outcome, prognosis and targeted therapy of gastric cancer patients.

The F5 gene predicts poor prognosis of patients with gastric cancer by promoting cell migration identified using a weighted gene co-expression network analysis

Distal gastric cancer(DGC)is a subgroup of gastric cancer(GC),which has different molecular characteristics from proximal gastric cancer(PGC).These differences result in different overall survival(OS)rates;however,data pertaining to the survival rate in PGC or DGC are contradictory.This suggests that the location of GC is not the unique cause of the different survival rates,while the molecular characteristics might be more important factors determining the prognosis of DGC.Therefore,the aim of this study was to discover key prognostic factors in DGC using bioinformatic methods and to explore the potential molecular mechanism.The Cancer Genome Atlas(TCGA)public database was employed to screen data relating to DGC,and we conducted a weighted gene co-expression network analysis(WGCNA)on DGC patient samples to establish co-expression modules.High-weight genes(hub genes)in a dominant color module were identified.In vitro experiments and gene set enrichment analyses(GSEA)were carried out to elucidate the potential molecular mechanism.In this study,139 DGC samples were enrolled to perform a co-expression analysis.According to the correlation between gene modules and clinical characteristics,the royal blue module related to stage M of DGC was screened,and a survival analysis was conducted to show that highcoagulation-factor V(F5)expression was related to the short OS of patients with GC.In vitro experiments confirmed that F5 could promote the migration of GC cells.GSEA suggested that F5 might have affected the prognosis of GC by modulating the activities of the Wnt and/or the TGF-βsignaling pathways.Our results indicated that high F5 expression predicts poor prognosis of patients with DGC,and it functions probably by promoting cell migration through the Wnt and/or the TGF-βsignaling pathways.

Overexpression of AMPD2 indicates poor prognosis in colorectal cancer patients via the Notch3 signaling pathway

BACKGROUND AMPD2 is a critical enzyme catalyzing smooth muscle energy supply and metabolism;however,its cellular biological function and clinical implication in colorectal cancer(CRC)are largely unknown.AIM To clarify the role of AMPD2 in CRC and study the pathway and prognostic value of its role.METHODS AMPD2 expression was analyzed by integrated bioinformatics analysis based on TCGA data sets and immunohistochemistry in tissue microarrays,and the correlation between AMPD2 expression and clinicopathological parameters,Notch3 expression,and prognostic features was assessed.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis were then performed to investigate the regulatory pathway involved.The effects of AMPD2 expression on CRC cells and Notch3 protein expression were investigated by downregulation and overexpression of AMPD2.RESULTS AMPD2 mRNA was significantly overexpressed in tumor tissue when compared with normal tissue in a cohort of the TCGA-COAD data set.Biological function enrichment analysis indicated that the Notch pathway strongly correlated with AMPD2 expression,and that the expression of Notch3 and JAG2 mRNA was positively associated with AMPD2 in CRC tissues.In vitro,AMPD2 overexpression markedly reduced Notch3 protein expression in CRC cells,while knockdown of AMPD2 showed the opposite findings.In addition,protein expression was significantly up-regulated in our CRC cohort as indicated by tissue microarray analysis.High expression of AMPD2 protein correlated with advanced depth of tumor and poor differentiation.Furthermore,high AMPD2 expression in CRC tissues was an indicator of poor outcome for CRC patients.CONCLUSION AMPD2 is commonly overexpressed in CRC,and acts as a metabolism oncogene to induce CRC progression through the Notch signaling pathway.Thus,AMPD2 may be a novel prognostic biomarker for CRC.

Elevated nuclear phospho-eIF4E body levels are associated with tumor progression and poor prognosis for acute myeloid leukemia

Uncontrolled proliferation is a hallmark of cancer cells,yet the molecular mechanisms that contribute to this proliferation are unclear.Therapeutic treatment of cancer is suboptimal in many cases,with no accurate index by which to evaluate the success of treatment or patient prognosis.In this study,we explored the protein levels of nuclear phospho-eIF4E in acute myeloid leukemia(AML)cell lines and primary leukemia samples by Western blot and immunofluorescence and as well analyzed transcriptomes by RNA-seq.We found nuclear phospho-eIF4E,an exporter of oncogenic mRNAs,to be abundant in AML.Further,nuclear phospho-eIF4E abundance was significantly associated with tumor burden as well as the response of AML patients to chemotherapy.The results demonstrate“massive clustering and export of oncogenic mRNAs to the translation machinery”by highly abundant RNA-nuclear phospho-eIF4E bodies.This is an efficient mechanism that may drive the proliferation of cancer cells.Herein,nuclear phospho-eIF4E bodies were identified as potential markers of AML,which may be useful for prognosis and as targets for cancer therapy.

Increased MAD2L2 expression predicts poor clinical outcome in Colon Adenocarcinoma

Background:Colon adenocarcinoma(COAD)is the second leading cause of cancer death worldwide thus,identification of COAD biomarkers is critical.Mitotic Arrest Deficient 2 Like 2(MAD2L2)is a key factor in mammalian DNA damage repair and is highly expressed in many malignant tumors.This is a comprehensive study of MAD2L2 expression,its diagnostic value,prognostic analysis,potential biological function,and impact on the immune system of patients with COAD.Methods:Gene expression,clinical relevance,prognostic analysis,diagnostic value,GO/KEGG cluster analysis,data obtained from TCGA,and bioinformatics statistical analysis were performed using the R package.Immune responses to MAD2L2 expression in COAD were analyzed using TIMER.The expression of MAD2L2 in HCT116 cells induced by the inflammatory factor TNF-αwas detected using Western blot.Results:Our results underscore the clinical diagnostic value and potential biological significance of MAD2L2 in patients with COAD.A high level of MAD2L2 expression has been found in COAD and correlated with tumor status and colon polyps.ROC curve analysis showed that MAD2L2 expression has high diagnostic value in COAD.Analysis of immune infiltration results showed that MAD2L2 expression was positively correlated with neutrophil levels.The western blot results demonstrated that MAD2L2 was dose-dependently present with TNF-α.GO/KEGG revealed that MAD2L2 overexpressed and coexpressed genes were mostly involved in biological functions,including hypoxia response,response to reduced oxygen levels,mitochondrial translation elongation,and other processes.Conclusion:MAD2L2 as a new COAD biomarker contributes to our understanding of how alterations in gene expression and the immunological environment contribute to the development of colon cancer.Following further investigation,MAD2L2 may prove to be a viable target factor for clinical diagnosis and therapy of COAD.

The Role of 1q21 Gain on the Prognosis of Multiple Myeloma

Multiple myeloma(MM)is a clonal expansion of malignant plasma cells,and comprises approximately 10%of hematologic malignancies.Although various therapeutic agents and strategies,such as immunomodulatory agents,proteasome inhibitors,monoclonal antibodies and hematopoietic stem cell transplantation(HSCT)have been evaluated,MM remains largely incurable.It is therefore important to further explore the risk factors for disease progression,and to design trials aimed at improving the patient outcomes.Previous studies have considered the presence of a gain in 1q21 as a risk factor for a poorer overall survival.Gain of 1q21 is one of the most common chromosomal aberrations in MM,being detected by fluorescence in situ hybridization in 36%to 47%of newly-diagnosed patients,as well as 52%and 62%patients with relapsed MM.Although a series of reports identified 1q21 gain in MM as a significant and independent poor prognostic factor,other studies failed to demonstrate any prognostic value.Thus,the prognostic value of 1q21 gain in MM remains controversial.We reviewed the current knowledge about 1q21 gain and its value for the clinical management of MM.

病毒性脑炎患者预后不良的危险因素分析

目的探讨病毒性脑炎患者预后不良危险因素。方法以医院2019年6月至2022年5月收治的259例病毒性脑炎患者为研究对象,根据预后情况将患者分为预后不良组(79例)和预后良好组(180例)。比较两组一般临床资料[性别、年龄、偏瘫、发热、低钠血症、低钾血症、住院时间、发病至住院时间、脑电图情况、脑膜刺激征、血肌酐(Scr)、血尿素氮(BUN)、谷丙转氨酶(GPT)、谷草转氨酶(GOT)、血清增殖诱导配体(APRIL)、血清B淋巴细胞刺激因子(BlyS)、血清T细胞正常表达和分泌刺激因子(RANTES)、血清纤维胶凝蛋白3(FCN3)、血清陷窝蛋白1(Caveolin-1)、血清基质金属蛋白酶-2(MMP-2)],logistic多因素回归分析病毒性脑炎患者预后不良的危险因素,采用受试者工作特征(ROC)曲线分析血清APRIL、BlyS、RANTES、FCN3、Caveolin-1、MMP-2水平联合检测对病毒性脑炎患者预后不良的预测价值。结果预后不良组血清APRIL、BlyS、RANTES、FCN3、Caveolin-1、MMP-2水平高于预后良好组(P<0.05);logistic回归分析显示,血清APRIL(>7.48μg·L^(-1))、BlyS(>7.14μg·L^(-1))、RANTES(>273.64 ng·L^(-1))、FCN3(>17.02 mg·L^(-1))、Caveolin-1(>15.62μg·L^(-1))、MMP-2(>496.13 ng·L^(-1))水平是病毒性脑炎患者预后不良的危险因素(P<0.05);ROC曲线结果显示,血清APRIL、BlyS、RANTES、FCN3、Caveolin-1、MMP-2水平联合预测病毒性脑炎患者预后不良的曲线下面积为0.804,最佳预测敏感度为92.41%,特异度为68.33%。结论病毒性脑炎患者预后与血清APRIL、BlyS、RANTES、FCN3、Caveolin-1、MMP-2水平存在关联性,上述血清联合应用时可有效预测预后不良发生风险,便于临床早期制定防治措施。

脓毒症合并凝血功能障碍患儿近期预后不良的危险因素

目的分析脓毒症合并凝血功能障碍患儿近期预后不良危险因素。方法回顾性选取郑州大学第一附属医院2021年9月至2023年8月收治的226例脓毒症合并凝血功能障碍患儿临床资料作为研究对象,根据患儿28 d预后情况分为预后不良组(34例)和预后良好组(192例)。比较两组一般资料及各项指标,筛选预后不良危险因素,评价各危险因素对预后不良预测价值。结果预后不良组血清纤维蛋白原(Fib)、抗凝血酶Ⅲ(AT-Ⅲ)水平低于预后良好组,急性生理与慢性健康状况评分系统(APACHEⅡ)分值高于预后良好组(P<0.05);Fib、AT-Ⅲ是脓毒症合并凝血功能障碍近期预后不良的保护因素,APACHEⅡ是脓毒症合并凝血功能障碍近期预后不良的独立危险因素(P<0.05);Fib、APACHEⅡ、AT-Ⅲ联合预测脓毒症合并凝血功能障碍患儿近期预后不良的曲线下面积(AUC)值高于Fib、APACHEⅡ、AT-Ⅲ单项预测(P<0.05);Kaplan-Meier曲线显示,Fib>1.67 g·L^(-1)、APACHEⅡ≤13.00分、AT-Ⅲ>38.56%患儿生存时间均长于Fib≤1.67 g·L^(-1)、APACHEⅡ>13.00分、AT-Ⅲ≤38.56%患儿(P<0.05)。结论Fib、AT-Ⅲ是脓毒症合并凝血功能障碍近期预后不良保护因素,APACHEⅡ是脓毒症合并凝血功能障碍近期预后不良的危险因素,各指标联合预测脓毒症合并凝血功能障碍近期预后不良价值好,临床可应用推广。

介入取栓治疗急性缺血性脑卒中预后不良的临床特征与风险因素分析

目的分析介入取栓治疗急性缺血性脑卒中(acute ischemic stroke,AIS)预后不良的临床特征及风险因素。方法回顾性分析172例AIS病例资料,均行介入取栓治疗。术后随访3个月,预后情况根据改良Rankin量表(modified Rankin scale,mRS)分为预后不良组(mRS 3~5分)69例和预后良好组(mRS 0~2分)103例。通过单因素及多因素Logistic分析,研究AIS患者介入取栓治疗预后不良的临床特征及风险因素。结果术后随访3个月,预后不良组69例,发生率40.12%。与预后良好组比较,预后不良组年龄>60岁比例更高,发病至入院时间、术前美国国立卫生院卒中量表(national institute of health stroke scale,NIHSS)评分、术前Alberta急性脑卒中分级早期CT(Alberta stroke program early CT,ASPECT)评分、取栓次数、入院时血糖水平、入院时同型半胱氨酸(Hcy)水平更高(均P<0.05)。多因素Logistic分析结果显示:AIS介入取栓治疗预后不良的危险因素包括发病至入院时间延长、术前NIHSS评分、术前ASPECT评分、入院时血糖水平升高(OR分别为1.813、1.990、1.782、2.335,均P<0.05)。结论AIS患者介入取栓治疗预后不良的危险因素包括发病至入院时间延长,NIHSS评分、ASPECT评分、血糖水平升高,可据此筛选具备低风险因素的患者进行干预,针对性制定预防措施,进而改善患者预后。

中央型肺栓塞短期不良预后危险因素及Charlson合并症指数的预测价值

目的探讨中央型肺栓塞(PE)患者短期不良预后危险因素及Charlson合并症指数(CCI)的预测价值。方法回顾性分析115例中央型PE患者,根据住院期间不良预后结果,将观察对象分为发生不良事件组和未发生不良事件组,分析不良事件组临床特征,对两组患者收集危险因素、CCI、血栓位置分组评分并进行单因素分析,对于有统计学意义的指标进行多因素Logistic回归分析。结果中央型PE患者临床症状以胸闷或呼吸困难最为常见(77.4%),其余依次为咳嗽(35.7%)、胸痛(28.7%)、晕厥(9.6%)、咯血(7.8%)。两组间性别、吸烟史、饮酒史、症状及体征差异无统计学意义;在单因素分析中,CCI、血栓位置分组评分、白细胞计数、中性粒细胞计数、尿素氮与中央型PE患者发生不良事件有关(P<0.05),多因素Logistic回归分析后,中性粒细胞计数升高(OR=1.494,95%CI:1.073~2.080,P=0.017)为独立危险因素(P<0.05)。发生不良事件组CCI高于未发生不良事件组(P=0.004),多因素分析显示CCI升高(OR=1.342,95%CI:1.022~1.763,P=0.034)为独立危险因素,且CCI每增加1分,发生不良事件风险增加34.2%。发生不良事件组血栓位置分组评分显著高于未发生不良事件组(OR=2.586,95%CI:1.366~4.896,P=0.004),且血栓位置分组评分每增加1分,发生不良事件风险增加1.586倍。结论中性粒细胞计数升高、CCI升高、血栓位置分组评分升高与中央型PE患者短期发生不良预后有关。