Development of a prognostic scoring system for hepatic vena cava Budd-Chiari syndrome with hepatocellular carcinoma

Background:Hepatocellular carcinoma(HCC)is a serious complication of hepatic vena cava Budd-Chiari syndrome(HVC-BCS)that significantly reduces the survival time of patients.Our study aimed to analyze the prognostic factors influencing the survival of HVC-BCS patients with HCC and to develop a prognostic scoring system.Methods:The clinical and follow-up data of 64 HVC-BCS patients with HCC who received invasive treatment at the First Affiliated Hospital of Zhengzhou University between January 2015 and December 2019 were retrospectively analyzed.Kaplan-Meier curves and log-rank tests were used to analyze the survival curve of patients and the difference in prognoses between the groups.Univariate and multivariate Cox regression analyses were performed to analyze the influence of biochemical,tumor,and etiological characteristics on the total survival time of patients,and a new prognostic scoring system was developed according to the regression coefficients of the independent predictors in the statistical model.The prediction efficiency was evaluated using the time-dependent receiver operating characteristics curve and concordance index.Results:Multivariate analysis showed that serum albumin level<34 g/L[hazard ratio(HR)=4.207,95%confidence interval(CI):1.816-8.932,P=0.001],maximum tumor diameter>7 cm(HR=8.623,95%CI:3.771-19.715,P<0.001),and inferior vena cava stenosis(HR=3.612,95%CI:1.646-7.928,P=0.001)were independent predictors of survival.A prognostic scoring system was developed according to the above-mentioned independent predictors,and patients were classified into grades A,B,C and D.Significant differences in survival were found among the four groups.Conclusions:This study successfully developed a prognostic scoring system for HVC-BCS patients with HCC,which is helpful for clinical evaluation of patient prognosis.

Identification and validation of a pyroptosis-related prognostic model for colorectal cancer based on bulk and single-cell RNA sequencing data

BACKGROUND Pyroptosis impacts the development of malignant tumors,yet its role in colorectal cancer(CRC)prognosis remains uncertain.AIM To assess the prognostic significance of pyroptosis-related genes and their association with CRC immune infiltration.METHODS Gene expression data were obtained from The Cancer Genome Atlas(TCGA)and single-cell RNA sequencing dataset GSE178341 from the Gene Expression Omnibus(GEO).Pyroptosis-related gene expression in cell clusters was analyzed,and enrichment analysis was conducted.A pyroptosis-related risk model was developed using the LASSO regression algorithm,with prediction accuracy assessed through K-M and receiver operating characteristic analyses.A nomo-gram predicting survival was created,and the correlation between the risk model and immune infiltration was analyzed using CIBERSORTx calculations.Finally,the differential expression of the 8 prognostic genes between CRC and normal samples was verified by analyzing TCGA-COADREAD data from the UCSC database.RESULTS An effective pyroptosis-related risk model was constructed using 8 genes-CHMP2B,SDHB,BST2,UBE2D2,GJA1,AIM2,PDCD6IP,and SEZ6L2(P<0.05).Seven of these genes exhibited differential expression between CRC and normal samples based on TCGA database analysis(P<0.05).Patients with higher risk scores demonstrated increased death risk and reduced overall survival(P<0.05).Significant differences in immune infiltration were observed between low-and high-risk groups,correlating with pyroptosis-related gene expression.CONCLUSION We developed a pyroptosis-related prognostic model for CRC,affirming its correlation with immune infiltration.This model may prove useful for CRC prognostic evaluation.

Establishment and evaluation of a prognostic model for patients with unresectable gastric cancer liver metastases

BACKGROUND Liver metastases(LM)is the primary factor contributing to unfavorable outcomes in patients diagnosed with gastric cancer(GC).The objective of this study is to analyze significant prognostic risk factors for patients with GCLM and develop a reliable nomogram model that can accurately predict individualized prognosis,thereby enhancing the ability to evaluate patient outcomes.AIM To analyze prognostic risk factors for GCLM and develop a reliable nomogram model to accurately predict individualized prognosis,thereby enhancing patient outcome assessment.METHODS Retrospective analysis was conducted on clinical data pertaining to GCLM(type III),admitted to the Department of General Surgery across multiple centers of the Chinese PLA General Hospital from January 2010 to January 2018.The dataset was divided into a development cohort and validation cohort in a ratio of 2:1.In the development cohort,we utilized univariate and multivariate Cox regression analyses to identify independent risk factors associated with overall survival in GCLM patients.Subsequently,we established a prediction model based on these findings and evaluated its performance using receiver operator characteristic curve analysis,calibration curves,and clinical decision curves.A nomogram was created to visually represent the prediction model,which was then externally validated using the validation cohort.RESULTS A total of 372 patients were included in this study,comprising 248 individuals in the development cohort and 124 individuals in the validation cohort.Based on Cox analysis results,our final prediction model incorporated five independent risk factors including albumin levels,primary tumor size,presence of extrahepatic metastases,surgical treatment status,and chemotherapy administration.The 1-,3-,and 5-years Area Under the Curve values in the development cohort are 0.753,0.859,and 0.909,respectively;whereas in the validation cohort,they are observed to be 0.772,0.848,and 0.923.Furthermore,the calibration curves demonstrated excellent consistency between observed values and actual values.Finally,the decision curve analysis curve indicated substantial net clinical benefit.CONCLUSION Our study identified significant prognostic risk factors for GCLM and developed a reliable nomogram model,demonstrating promising predictive accuracy and potential clinical benefit in evaluating patient outcomes.

Use of machine learning models for the prognostication of liver transplantation: A systematic review

BACKGROUND Liver transplantation(LT)is a life-saving intervention for patients with end-stage liver disease.However,the equitable allocation of scarce donor organs remains a formidable challenge.Prognostic tools are pivotal in identifying the most suitable transplant candidates.Traditionally,scoring systems like the model for end-stage liver disease have been instrumental in this process.Nevertheless,the landscape of prognostication is undergoing a transformation with the integration of machine learning(ML)and artificial intelligence models.AIM To assess the utility of ML models in prognostication for LT,comparing their performance and reliability to established traditional scoring systems.METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines,we conducted a thorough and standardized literature search using the PubMed/MEDLINE database.Our search imposed no restrictions on publication year,age,or gender.Exclusion criteria encompassed non-English studies,review articles,case reports,conference papers,studies with missing data,or those exhibiting evident methodological flaws.RESULTS Our search yielded a total of 64 articles,with 23 meeting the inclusion criteria.Among the selected studies,60.8%originated from the United States and China combined.Only one pediatric study met the criteria.Notably,91%of the studies were published within the past five years.ML models consistently demonstrated satisfactory to excellent area under the receiver operating characteristic curve values(ranging from 0.6 to 1)across all studies,surpassing the performance of traditional scoring systems.Random forest exhibited superior predictive capabilities for 90-d mortality following LT,sepsis,and acute kidney injury(AKI).In contrast,gradient boosting excelled in predicting the risk of graft-versus-host disease,pneumonia,and AKI.CONCLUSION This study underscores the potential of ML models in guiding decisions related to allograft allocation and LT,marking a significant evolution in the field of prognostication.

A Meta-Analysis of the Prognostic and Clinicopathological Significance of circZFR in Human Gastrointestinal Cancers

Background: Studies of gastrointestinal (GIT) cancers have shown that circZFR could be involved in the development and progression of various GIT cancers. However, small sample sizes limit the clinical significance of these studies. Here, a meta-analysis was conducted to ascertain the actual involvement of circZFR in the development and prognosis of GIT cancers. Methods: PubMed, Embase, Web of Science, and the Cochrane Library were searched up to December 31, 2023. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were pooled to evaluate the association between circZFR expression and overall survival (OS). Publication bias was measured using the funnel plot and Egger’s test. Results: 10 studies having 659 participants were enrolled for meta-analysis. High circZFR expression was associated with poor OS (HR = 1.4, 95% CI: 1.20, 1.70). High circZFR expression also predicted larger tumor size (OR = 4.38, 95% CI 2.65, 7.25), advanced clinical stage (OR = 5.33, 95% CI 3.10, 9.16), and tendency for distant metastasis (OR = 2.89, 95% CI: 1.62, 5.11), but was not related to age, gender, and histological grade. Conclusions: In summary, high circZFR expression was associated with poor OS, larger tumor size, advanced stage cancer and tendency for distant metastasis. These findings suggested that circZFR could be a prognostic marker for GIT cancers.

A Prognostic Model Based on Colony Stimulating Factors-related Genes in Triple-negative Breast Cancer

Objective Triple-negative breast cancer(TNBC)is the breast cancer subtype with the worst prognosis,and lacks effective therapeutic targets.Colony stimulating factors(CSFs)are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells,playing an important role in the malignant progression of TNBC.This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes(CRGs),and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy.Methods We downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database.Through LASSO Cox regression analysis,we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score(CRRS).We further analyzed the correlation between CRRS and patient prognosis,clinical features,tumor microenvironment(TME)in both high-risk and low-risk groups,and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy.Results We identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model.Kaplan-Meier survival curves,time-dependent receiver operating characteristic curves,and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival,and the predictive ability of CRRS prognostic model was further validated using the GEO dataset.Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients.Moreover,patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil,ipatasertib,and paclitaxel.Conclusion We have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs,which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment.Moreover,the key genes within this model may represent potential molecular targets for future therapies of TNBC.

A pilot clinical study to evaluate feasibility of using single patient classifier as a prognostic test in stage Ⅱ-Ⅲ gastric cancer patients

Objective:Precision medicine approaches emphasize the importance of reliable prognostic tools for guiding individualized therapy decisions.In this study,we evaluated the clinical feasibility of the single patient classifier(SPC)test,a new clinical-grade prognostic assay,in stageⅡ-Ⅲgastric cancer patients.Methods:A prospective multicenter study was conducted,involving 237 patients who underwent gastrectomy between September 2019 and August 2020 across nine hospitals.The SPC test was employed to stratify patients into risk groups,and its feasibility and performance were evaluated.The primary endpoint was the proportion of the cases in which the test results were timely delivered before selecting postoperative treatment.Furthermore,3-year disease-free survivals of risk groups were analyzed.Results:The SPC test met the primary endpoint criteria.The 99.5%of SPC tests were timely delivered to hospitals before the postoperative treatment started.In a clinical setting,the median time from the specimen transfer to laboratory to the result delivery to hospital was 4 d.Furthermore,3-year disease-free survivals were significantly different between risk groups classified with SPC tests.Conclusions:This study highlights the SPC test's feasibility in offering crucial information timely delivered for making informed decisions regarding postoperative treatment strategies.It also provides evidence to support the implementation of a future prospective clinical trial aimed at evaluating the clinical utility of the SPC test in guiding personalized treatment decisions for gastric cancer patients.

Advancing prognostic precision in gastric cancer with an immunoinflammatory index

Gastric cancer remains a major global health challenge with high morbidity and mortality rates.Recent advancements in immunology and inflammation research have highlighted the crucial roles that these biological processes play in tumor progression and patient outcomes.This has sparked new interest in developing prognostic biomarkers that integrate these two key biological processes.In this letter,we discuss the recent study by Ba et al,which proposed a novel prognostic immunoinflammatory index for patients with gastric cancer.We underscore the importance of this research,its potential impact on medical practice,and the prospective avenues for further investigation in this rapidly emerging area of study.

Validation of prognostic scores for predicting acute liver failure and in-hospital death in patients with dengue-induced severe hepatitis

BACKGROUND Acute liver failure(ALF)in dengue is rare but fatal.Early identification of patients who are at risk of ALF is the key strategy to improve survival.AIM To validate prognostic scores for predicting ALF and in-hospital mortality in dengue-induced severe hepatitis(DISH).METHODS We retrospectively reviewed 2532 dengue patients over a period of 16 years(2007-2022).Patients with DISH,defined as transaminases>10 times the normal reference level and DISH with subsequent ALF,were included.Univariate regre-ssion analysis was used to identify factors associated with outcomes.Youden’s index in conjunction with receiver operating characteristic(ROC)analysis was used to determine optimal cut-off values for prognostic scores in predicting ALF and in-hospital death.Area under the ROC(AUROC)curve values were compared using paired data nonparametric ROC curve estimation.RESULTS Of 193 DISH patients,20 developed ALF(0.79%),with a mortality rate of 60.0%.International normalized ratio,bilirubin,albumin,and creatinine were indepen-dent predictors associated with ALF and death.Prognostic scores showed excel-lent performance:Model for end-stage liver disease(MELD)score≥15 predicted ALF(AUROC 0.917,sensitivity 90.0%,specificity 88.4%)and≥18 predicted death(AUROC 0.823,sensitivity 86.9%,specificity 89.1%);easy albumin-bilirubin(ALBI)score≥-30 predicted ALF and death(ALF:AUROC 0.835,sensitivity80.0%,specificity 72.2%;death:AUROC 0.808,sensitivity 76.9%,specificity 69.3%);ALBI score≥-2 predicted ALF and death(ALF:AUROC 0.806,sensitivity 80.0%,specificity 77.4%;death:AUROC 0.799,sensitivity 76.9%,specificity 74.3%).Platelet-ALBI score also showed good performance in predicting ALF and death(AUROC=0.786 and 0.699,respectively).MELD and EZ-ALBI scores had similar performance in predicting ALF(Z=1.688,P=0.091)and death(Z=0.322,P=0.747).CONCLUSION MELD score is the best predictor of ALF and death in DISH patients.EZ-ALBI score,a simpler yet effective score,shows promise as an alternative prognostic tool in dengue patients.

Construction and validation of a pancreatic cancer prognostic model based on genes related to the hypoxic tumor microenvironment

BACKGROUND Pancreatic cancer is one of the most lethal malignancies,characterized by poor prognosis and low survival rates.Traditional prognostic factors for pancreatic cancer offer inadequate predictive accuracy,often failing to capture the complexity of the disease.The hypoxic tumor microenvironment has been recognized as a significant factor influencing cancer progression and resistance to treatment.This study aims to develop a prognostic model based on key hypoxia-related molecules to enhance prediction accuracy for patient outcomes and to guide more effective treatment strategies in pancreatic cancer.AIM To develop and validate a prognostic model for predicting outcomes in patients with pancreatic cancer using key hypoxia-related molecules.METHODS This pancreatic cancer prognostic model was developed based on the expression levels of the hypoxia-associated genes CAPN2,PLAU,and CCNA2.The results were validated in an independent dataset.This study also examined the correlations between the model risk score and various clinical features,components of the immune microenvironment,chemotherapeutic drug sensitivity,and metabolism-related pathways.Real-time quantitative PCR verification was conducted to confirm the differential expression of the target genes in hypoxic and normal pancreatic cancer cell lines.RESULTS The prognostic model demonstrated significant predictive value,with the risk score showing a strong correlation with clinical features:It was significantly associated with tumor grade(G)(bP<0.01),moderately associated with tumor stage(T)(aP<0.05),and significantly correlated with residual tumor(R)status(bP<0.01).There was also a significant negative correlation between the risk score and the half-maximal inhibitory concentration of some chemotherapeutic drugs.Furthermore,the risk score was linked to the enrichment of metabolism-related pathways in pancreatic cancer.CONCLUSION The prognostic model based on hypoxia-related genes effectively predicts pancreatic cancer outcomes with improved accuracy over traditional factors and can guide treatment selection based on risk assessment.

Clinical features and prognostic factors of duodenal neuroendocrine tumours:A comparative study of ampullary and nonampullary regions

BACKGROUND Duodenal neuroendocrine tumours(DNETs)are rare neoplasms.However,the incidence of DNETs has been increasing in recent years,especially as an incidental finding during endoscopic studies.Regrettably,there is no consensus regarding the ideal treatment of DNETs.Even there are few studies on the clinical features and survival analysis of DNETs.AIM To analyze the clinical characteristics and prognostic factors of patients with duodenal neuroendocrine tumours.METHODS The clinical data of DNETs diagnosed in the First Affiliated Hospital of Air Force Military Medical University from June 2011 to July 2022 were collected.Neuroen-docrine tumours located in the ampulla area of the duodenum were divided into the ampullary region group;neuroendocrine tumours in any part of the duo-denum outside the ampullary area were divided into the nonampullary region group.Using a retrospective study,the clinical characteristics of the two groups and risk factors affecting the survival of DNET patients were analysed.RESULTS Twenty-nine DNET patients were screened.The male to female ratio was 1:1.9,and females comprised the majority.The ampullary region group accounted for 24.1%(7/29),while the nonampullary region group accounted for 75.9%(22/29).When diagnosed,the clinical symptoms of the ampullary region group were mainly abdominal pain(85.7%),while those of the nonampullary region groups were mainly abdominal distension(59.1%).There were differences in the composition of staging of tumours between the two groups(Fisher's exact probability method,P=0.001),with nonampullary stage II tumours(68.2%)being the main stage(P<0.05).After the diagnosis of DNETs,the survival rate of the ampullary region group was 14.3%(1/7),which was lower than that of 72.7%(16/22)in the nonampullary region group(Fisher's exact probability method,P=0.011).The survival time of the ampullary region group was shorter than that of the nonampullary region group(P<0.000).The median survival time of the ampullary region group was 10.0 months and that of the nonampullary region group was 451.0 months.Multivariate analysis showed that tumours in the ampulla region and no surgical treatment after diagnosis were independent risk factors for the survival of DNET patients(HR=0.029,95%CI 0.004-0.199,P<0.000;HR=12.609,95%CI:2.889-55.037,P=0.001).Further analysis of nonampullary DNET patients showed that the survival time of patients with a tumour diameter<2 cm was longer than that of patients with a tumour diameter≥2 cm(t=7.243,P=0.048).As of follow-up,6 patients who died of nonampullary DNETs had a tumour diameter that was≥2 cm,and 3 patients in stage IV had liver metastasis.Patients with a tumour diameter<2 cm underwent surgical treatment,and all survived after surgery.CONCLUSION Surgical treatment is a protective factor for prolonging the survival of DNET patients.Compared to DNETs in the ampullary region,patients in the nonampullary region group had a longer survival period.The liver is the organ most susceptible to distant metastasis of nonampullary DNETs.

A comprehensive and systematic analysis of Dihydrolipoamide S-acetyltransferase (DLAT) as a novel prognostic biomarker in pan-cancer and glioma

Background:Dihydrolipoamide S-acetyltransferase(DLAT)is a subunit of the pyruvate dehydrogenase complex(PDC),a rate-limiting enzyme complex,that can participate in either glycolysis or the tricarboxylic acid cycle(TCA).However,the pathogenesis is not fully understood.We aimed to perform a more systematic and comprehensive analysis of DLAT in the occurrence and progression of tumors,and to investigate its function in patients’prognosis and immunotherapy.Methods:The differential expression,diagnosis,prognosis,genetic and epigenetic alterations,tumor microenvironment,stemness,immune infiltration cells,function enrichment,single-cell analysis,and drug response across cancers were conducted based on multiple computational tools.Additionally,we validated its carcinogenic effect and possible mechanism in glioma cells.Results:We exhibited that DLAT expression was increased in most tumors,especially in glioma,and affected the survival of tumor patients.DLAT was related to RNA modification genes,DNA methylation,immune infiltration,and immune infiltration cells,including CD4+T cells,CD8+T cells,Tregs,and cancer-associatedfibroblasts.Single-cell analysis displayed that DLAT might regulate cancer by mediating angiogenesis,inflammation,and stemness.Enrichment analysis revealed that DLAT might take part in the cell cycle pathway.Increased expression of DLAT leads tumor cells to be more resistant to many kinds of compounds,including PI3Kβinhibitors,PKC inhibitors,HSP90 inhibitors,and MEK inhibitors.In addition,glioma cells with DLAT silence inhibited proliferation,migration,and invasion ability,and promoted cell apoptosis.Conclusion:We conducted a comprehensive analysis of DLAT in the occurrence and progression of tumors,and its possible functions and mechanisms.DLAT is a potential diagnostic,prognostic,and immunotherapeutic biomarker for cancer patients.

Systemic Inflammation Response Index and weight loss as prognostic factors in metastatic pancreatic cancer: A concept study from the PANTHEIA-SEOM trial

BACKGROUND The prognostic value of the Systemic Inflammation Response Index(SIRI)in advanced pancreatic cancer is recognized,but its correlation with patients´nutritional status and outcomes remains unexplored.AIM To study the prognostic significance of SIRI and weight loss in metastatic pancreatic cancer.METHODS The PANTHEIA-Spanish Society of Medical Oncology(SEOM)study is a multicentric(16 Spanish hospitals),observational,longitudinal,non-interventional initiative,promoted by the SEOM Real World-Evidence work group.This pilot study sought to analyze the association between weight loss and inflammatory status as defined by SIRI.The cohort stems from a proof-of-concept pilot study conducted at one of the coordinating centers.Patients with pathologically confirmed metastatic pancreatic adenocarcinoma,treated from January 2020 to January 2023,were included.The index was calculated using the product of neutrophil and monocyte counts,divided by lymphocyte counts,obtained within 15 days before initiation chemotherapy.This study evaluated associations between overall survival(OS),SIRI and weight loss.RESULTS A total of 50 patients were included.66%of these patients were male and the median age was 66 years.Metastasis sites:36%liver,12%peritoneal carcinomatosis,10%lung,and 42%multiple locations.Regarding the first line palliative chemotherapy treatments:50%received gemcitabine plus nab-paclitaxel;28%,modified fluorouracil,leucovorin,irinotecan and oxaliplatin,and 16%were administered gemcitabine.42%had a weight loss>5%in the three months(mo)preceding diagnosis.21 patients with a SIRI≥2.3×10^(3)/L exhibited a trend towards a lower median OS compared to those with a SIRI<2.3×10^(3)/L(4 vs 18 mo;P<0.000).Among 21 patients with>5%weight loss before diagnosis,the median OS was 6 mo,in contrast to 19 mo for those who did not experience such weight loss(P=0.003).Patients with a weight loss>5%showed higher SIRI levels.This difference was statistically significant(P<0.000).For patients with a SIRI<2.3×10^(3)/L,those who did not lose>5%of their weight had an OS of 20 mo,compared to 11 mo for those who did(P<0.001).No association was found between carbohydrate antigen 19-9 levels≥1000 U/mL and weight loss.CONCLUSION A higher SIRI was correlated with decreased survival rates in patients with metastatic pancreatic cancer and associated with weight loss.An elevated SIRI is suggested as a predictor of survival,emphasizing the need for prospective validation in the upcoming PANTHEIA-SEOM study.

Prognostic factors for lacrimal gland adenoid cystic carcinoma:a retrospective study in Chinese patients

AIM:To explore the prognostic factors for lacrimal gland adenoid cystic carcinoma(LGACC)in Chinese patients.METHODS:Clinical and histopathological data were reviewed in patients with pathologically confirmed LGACC.Local recurrence,metastasis,and disease-specific death were the main outcome measures.Univariate and multivariate analyses were performed by the Kaplan-Meier method and a Cox proportional hazard model.RESULTS:This retrospective cohort study included 45 patients with pathologically confirmed LGACC between January 2008 and June 2022.Tumor(T)classification(P=0.005),nodal metastasis(N)classification(P=0.018)and positive margin(P=0.008)were independent risk factors of recurrence;T(P=0.013)and N(P=0.003)classification and the basaloid tumor type(P=0.032)were independent risk factors for metastasis;T classification(P<0.001)was an independent factor of death of disease.In the further analysis,the durations from first surgery to radiotherapy is correlated with metastatic risk in LGACC patients with basaloid component(P=0.022).CONCLUSION:Histological subtype should be emphasized when evaluating prognosis and guiding treatment.Timely radiotherapy may reduce the risk of metastasis in patients with basaloid component.

sTREM-1 as promising prognostic biomarker for acute-on-chronic liver failure and mortality in patients with acute decompensation of cirrhosis

BACKGROUND Acute decompensation(AD)of cirrhosis is associated with high short-term mortality,mainly due to the development of acute-on-chronic liver failure(ACLF).Thus,there is a need for biomarkers for early and accurate identification of AD patients with high risk of development of ACLF and mortality.Soluble triggering receptor expressed on myeloid cells-1(sTREM-1)is released from activated innate immune cells and correlated with various inflammatory processes.AIM To explore the prognostic value of sTREM-1 in patients with AD of cirrhosis.METHODS A multicenter prospective cohort of 442 patients with cirrhosis hospitalized for AD was divided into a study cohort(n=309)and validation cohort(n=133).Demographic and clinical data were collected,and serum sTREM-1 was measured at admission.All enrolled patients were followed-up for at least 1 year.RESULTS In patients with AD and cirrhosis,serum sTREM-1 was an independent prognosis predictor for 1-year survival and correlated with liver,coagulation,cerebral and kidney failure.A new prognostic model of AD(P-AD)incorporating sTREM-1,blood urea nitrogen(BUN),total bilirubin(TBil),international normalized ratio(INR)and hepatic encephalopathy grades was established and performed better than the model for end-stage liver disease(MELD),MELD-sodium(MELD-Na),chronic liver failure-consortium(CLIF-C)ACLF and CLIF-C AD scores.Additionally,sTREM-1 was increased in ACLF and predicted the development of ACLF during first 28-d follow-up.The ACLF risk score incorporating serum sTREM-1,BUN,INR,TBil and aspartate aminotransferase levels was established and significantly superior to MELD,MELD-Na,CLIF-C ACLF,CLIF-C AD and P-AD in predicting risk of ACLF development.CONCLUSION Serum sTREM-1 is a promising prognostic biomarker for ACLF development and mortality in patients with AD of cirrhosis.

Identification of prognostic molecular subtypes and model based on CD8+ T cells for lung adenocarcinoma

Background:Cytotoxic T lymphocytes(CD8+T)cells function critically in mediating anti-tumor immune response in cancer patients.Characterizing the specific functions of CD8+T cells in lung adenocarcinoma(LUAD)could help better understand local anti-tumor immune responses and estimate the effect of immunotherapy.Methods:Gens related to CD8+T cells were identified by cluster analysis based on the single-cell sequencing data of three LUAD tissues and their paired normal tissues.Weighted gene co-expression network analysis(WGCNA),consensus clustering,differential expression analysis,least absolute shrinkage and selection operator(LASSO)and Cox regression analysis were conducted to classify molecular subtypes for LUAD and to develop a risk model using prognostic genes related to CD8+T cells.Expression of the genes in the prognostic model,their effects on tumor cell invasion,and interactions with CD8+T cells were verified by cell experiments.Results:This study defined two LUAD clusters(CD8+0 and CD8+1)based on CD8+T cells,with cluster CD8+0 being significantly associated with the prognosis of LUAD.Three heterogeneous subtypes(clusters 1,2,and 3)differing in prognosis,genome mutation events,and immune status were categorized using 42 prognostic genes.A prognostic model created based on 11 significant genes(including CD200R1,CLEC17A,ZC3H12D,GNG7,SNX30,CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2,and KRT81)was able to independently estimate the death risk for patients in different LUAD cohorts.Moreover,the model also showed general applicability in external validation cohorts.Low-risk patients could benefit more from taking immunotherapy and were significantly related to the resistance to anticancer drugs.The results from cell experiments demonstrated that the expression of CD200R1,CLEC17A,ZC3H12D,GNG7,and SNX30 was significantly downregulated,while that of CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2 and KRT81 was upregulated in LUAD cells.Inhibition of CD200R1 greatly increased the invasiveness of the LUAD cells,but inhibiting CDCP1 expression weakened the invasion ability of LUAD cells.Conclusion:This study defined two prognostic CD8+T cell clusters and classified three heterogeneous molecular subtypes for LUAD.A prognostic model predictive of the potential effects of immunotherapy on LUAD patients was developed.

Prognostic value of neutrophil-to-lymphocyte ratio in gastric cancer patients undergoing neoadjuvant chemotherapy:A systematic review and meta-analysis

BACKGROUND In recent studies,accumulating evidence has revealed a strong association between the inflammatory response and the prognosis of many tumors.There is a certain correlation of neutrophil-to-lymphocyte ratio(NLR)with the prognosis in gastric cancer(GC)patients undergoing neoadjuvant chemotherapy(NAC).However,the existing research results have remained controversial.AIM To explore the relationship between NLR ratio and prognosis of GC patients receiving NAC.METHODS A thorough systematic search was performed in databases such as PubMed,Embase,Web of Science,and Cochrane Library,the search is available until February 29,2024,and studies exploring the interaction of NLR with clinical outcomes were collected.Relevant studies meeting pre-defined inclusion and exclusion criteria were carefully chosen.The outcomes included progression-free survival(PFS),relapse-free survival,disease-free survival(DFS),and overall survival(OS).The hazard ratio(HR)and its corresponding 95%confidence interval(CI)were utilized for estimation.RESULTS Our analysis encompassed 852 patients and incorporated data from 12 cohort studies.The comprehensive analysis revealed a significant association of high NLR with reduced OS(HR=1.76;95%CI:1.22-2.54,P=0.003),relapsefree survival(HR=3.73;95%CI:1.74-7.96,P=0.0007),and PFS(HR=2.32;95%CI:1.42-3.81,P=0.0008)in patients.However,this correlation in disease-free survival was not significant.NLR demonstrated its crucial role in effectively predicting the OS of GC patients undergoing NAC at different detection times,ages,regions,and NLR thresholds.CONCLUSION In GC patients receiving NAC,an elevated NLR is strongly associated with reduced OS and PFS.NLR has become an effective biomarker for patient prognosis evaluation,providing valuable insights for the treatment strategies of NAC in GC patients.

Prognostic relevance of ventricular arrhythmias in surgical patients with gastrointestinal tumors

BACKGROUND Individuals diagnosed with gastrointestinal tumors are at an increased risk of developing cardiovascular diseases.Among which,ventricular arrhythmia is a prevalent clinical concern.This suggests that ventricular arrhythmias may have predictive value in the prognosis of patients with gastrointestinal tumors.AIM To explore the prognostic value of ventricular arrhythmias in patients with gastrointestinal tumors receiving surgery.METHODS We retrospectively analyzed data from 130 patients undergoing gastrointestinal tumor resection.These patients were evaluated by a 24-h ambulatory electrocardiogram(ECG)at the Sixth Affiliated Hospital of Sun Yat-sen University from January 2018 to June 2020.Additionally,41 general healthy age-matched and sexmatched controls were included.Patients were categorized into survival and non-survival groups.The primary endpoint was all-cause mortality,and secondary endpoints included major adverse cardiovascular events(MACEs).RESULTS Colorectal tumors comprised 90%of cases.Preoperative ambulatory ECG monitoring revealed that among the 130 patients with gastrointestinal tumors,100(76.92%)exhibited varying degrees of premature ventricular contractions(PVCs).Ten patients(7.69%)manifested non-sustained ventricular tachycardia(NSVT).The patients with gastrointestinal tumors exhibited higher PVCs compared to the healthy controls on both conventional ECG[27(21.3)vs 1(2.5),P=0.012]and 24-h ambulatory ECG[14(1.0,405)vs 1(0,6.5),P<0.001].Non-survivors had a higher PVC count than survivors[150.50(7.25,1690.50)vs 9(0,229.25),P=0.020].During the follow-up period,24 patients died and 11 patients experienced MACEs.Univariate analysis linked PVC>35/24 h to all-cause mortality,and NSVT was associated with MACE.However,neither PVC burden nor NSVT independently predicted outcomes according to multivariate analysis.CONCLUSION Patients with gastrointestinal tumors exhibited elevated PVCs.PVCs>35/24 h and NSVT detected by 24-h ambulatory ECG were prognostically significant but were not found to be independent predictors.

Risk factors,prognostic factors,and nomograms for distant metastasis in patients with diagnosed duodenal cancer:A population-based study

BACKGROUND Duodenal cancer is one of the most common subtypes of small intestinal cancer,and distant metastasis(DM)in this type of cancer still leads to poor prognosis.Although nomograms have recently been used in tumor areas,no studies have focused on the diagnostic and prognostic evaluation of DM in patients with primary duodenal cancer.AIM To develop and evaluate nomograms for predicting the risk of DM and person-alized prognosis in patients with duodenal cancer.METHODS Data on duodenal cancer patients diagnosed between 2010 and 2019 were extracted from the Surveillance,Epidemiology,and End Results database.Univariate and multivariate logistic regression analyses were used to identify independent risk factors for DM in patients with duodenal cancer,and univariate and multivariate Cox proportional hazards regression analyses were used to determine independent prognostic factors in duodenal cancer patients with DM.Two novel nomograms were established,and the results were evaluated by receiver operating characteristic(ROC)curves,calibration curves,and decision curve analysis(DCA).RESULTS A total of 2603 patients with duodenal cancer were included,of whom 457 cases(17.56%)had DM at the time of diagnosis.Logistic analysis revealed independent risk factors for DM in duodenal cancer patients,including gender,grade,tumor size,T stage,and N stage(P<0.05).Univariate and multivariate COX analyses further identified independent prognostic factors for duodenal cancer patients with DM,including age,histological type,T stage,tumor grade,tumor size,bone metastasis,chemotherapy,and surgery(P<0.05).The accuracy of the nomograms was validated in the training set,validation set,and expanded testing set using ROC curves,calibration curves,and DCA curves.The results of Kaplan-Meier survival curves(P<0.001)indicated that both nomograms accurately predicted the occurrence and prognosis of DM in patients with duodenal cancer.CONCLUSION The two nomograms are expected as effective tools for predicting DM risk in duodenal cancer patients and offering personalized prognosis predictions for those with DM,potentially enhancing clinical decision-making.

Hepatocellular carcinoma:An analysis of the expression status of stress granules and their prognostic value

BACKGROUND Hepatocellular carcinoma(HCC)is a global popular malignant tumor,which is difficult to cure,and the current treatment is limited.AIM To analyze the impacts of stress granule(SG)genes on overall survival(OS),survival time,and prognosis in HCC.METHODS The combined The Cancer Genome Atlas-Liver Hepatocellular Carcinoma(TCGA-LIHC),GSE25097,and GSE36376 datasets were utilized to obtain genetic and clinical information.Optimal hub gene numbers and corresponding coefficients were determined using the Least absolute shrinkage and selection operator model approach,and genes for constructing risk scores and corresponding correlation coefficients were calculated according to multivariate Cox regression,respectively.The prognostic model’s receiver operating characteristic(ROC)curve was produced and plotted utilizing the time ROC software package.Nomogram models were constructed to predict the outcomes at 1,3,and 5-year OS prognostications with good prediction accuracy.RESULTS We identified seven SG genes(DDX1,DKC1,BICC1,HNRNPUL1,CNOT6,DYRK3,CCDC124)having a prognostic significance and developed a risk score model.The findings of Kaplan-Meier analysis indicated that the group with a high risk exhibited significantly reduced OS in comparison with those of the low-risk group(P<0.001).The nomogram model’s findings indicate a significant enhancement in the accuracy of OS prediction for individuals with HCC in the TCGA-HCC cohort.Gene Ontology and Gene Set Enrichment Analysis suggested that these SGs might be involved in the cell cycle,RNA editing,and other biological processes.CONCLUSION Based on the impact of SG genes on HCC prognosis,in the future,it will be used as a biomarker as well as a unique therapeutic target for the identification and treatment of HCC.