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.

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 nutritional index in predicting survival of patients with gastric or gastroesophageal junction adenocarcinoma: A systematic review

BACKGROUND Gastric cancer is the third most common cause of cancer related death worldwide.Surgery with or without chemotherapy is the most common approach with curative intent;however,the prognosis is poor as mortality rates remain high.Several indexes have been proposed in the past few years in order to estimate the survival of patients undergoing gastrectomy.The preoperative nutritional status of gastric cancer patients has recently gained attention as a factor that could affect the postoperative course and various indexes have been developed.The aim of this systematic review was to assess the role of the prognostic nutritional index(PNI)in predicting the survival of patients with gastric or gastroesophageal adenocarcinoma who underwent gastrectomy with curative intent.AIM To investigate the role of PNI in predicting the survival of patients with gastric or gastroesophageal junction adenocarcinoma.METHODS A thorough literature search of PubMed and the Cochrane library was performed for studies comparing the overall survival(OS)of patients with gastric or gastroesophageal cancer after surgical resection depending on the preoperative PNI value.The PRISMA algorithm was used in the screening process and finally 16 studies were included in this systematic review.The review protocol was registered in the International Prospective Register of Systematic Reviews(PRO) RESULTS Sixteen studies involving 14551 patients with gastric or esophagogastric junction adenocarcinoma undergoing open or laparoscopic or robotic gastrectomy with or without adjuvant chemotherapy were included in this systematic review.The patients were divided into high-and low-PNI groups according to cut-off values that were set according to previous reports or by using receiver operating characteristic curve analysis in each individual study.The 5-year OS of patients in the low-PNI groups ranged between 39%and 70.6%,while in the high-PNI groups,it ranged between 54.9%and 95.8%.In most of the included studies,patients with high preoperative PNI showed statistically significant better OS than the low PNI groups.In multivariate analyses,low PNI was repeatedly recognised as an independent prognostic factor for poor survival.CONCLUSION According to the present study,low preoperative PNI seems to be an indicator of poor OS of patients undergoing gastrectomy for gastric or gastroesophageal cancer.

Prognostic value of preoperative immune-nutritional scoring systems in remnant gastric cancer patients undergoing surgery

BACKGROUND Remnant gastric cancer(GC)is defined as GC that occurs five years or more after gastrectomy.Systematically evaluating the preoperative immune and nutritional status of patients and analyzing its prognostic impact on postoperative remnant gastric cancer(RGC)patients are crucial.A simple scoring system that combines multiple immune or nutritional indicators to identify nutritional or immune status before surgery is necessary.AIM To evaluate the value of preoperative immune-nutritional scoring systems in predicting the prognosis of patients with RGC.METHODS The clinical data of 54 patients with RGC were collected and analyzed retrospectively.Prognostic nutritional index(PNI),controlled nutritional status(CONUT),and Naples prognostic score(NPS)were calculated by preoperative blood indicators,including absolute lymphocyte count,lymphocyte to monocyte ratio,neutrophil to lymphocyte ratio,serum albumin,and serum total cholesterol.Patients with RGC were divided into groups according to the immune-nutritional risk.The relationship between the three preoperative immune-nutritional scores and clinical characteristics was analyzed.Cox regression and Kaplan–Meier analysis was performed to analyze the difference in overall survival(OS)rate between various immune-nutritional score groups.RESULTS The median age of this cohort was 70.5 years(ranging from 39 to 87 years).No significant correlation was found between most pathological features and immune-nutritional status(P>0.05).Patients with a PNI score<45,CONUT score or NPS score≥3 were considered to be at high immune-nutritional risk.The areas under the receiver operating characteristic curves of PNI,CONUT,and NPS systems for predicting postoperative survival were 0.611[95%confidence interval(CI):0.460–0.763;P=0.161],0.635(95%CI:0.485–0.784;P=0.090),and 0.707(95%CI:0.566–0.848;P=0.009),respectively.Cox regression analysis showed that the three immunenutritional scoring systems were significantly correlated with OS(PNI:P=0.002;CONUT:P=0.039;NPS:P<0.001).Survival analysis revealed a significant difference in OS between different immune-nutritional groups(PNI:75 mo vs 42 mo,P=0.001;CONUT:69 mo vs 48 mo,P=0.033;NPS:77 mo vs 40 mo,P<0.001).CONCLUSION These preoperative immune-nutritional scores are reliable multidimensional prognostic scoring systems for predicting the prognosis of patients with RGC,in which the NPS system has relatively effective predictive performance.

An Edge-Fog-Cloud Computing-Based Digital Twin Model for Prognostics Health Management of Process Manufacturing Systems

The prognostics health management(PHM)fromthe systematic viewis critical to the healthy continuous operation of processmanufacturing systems(PMS),with different kinds of dynamic interference events.This paper proposes a three leveled digital twinmodel for the systematic PHMof PMSs.The unit-leveled digital twinmodel of each basic device unit of PMSs is constructed based on edge computing,which can provide real-time monitoring and analysis of the device status.The station-leveled digital twin models in the PMSs are designed to optimize and control the process parameters,which are deployed for the manufacturing execution on the fog server.The shop-leveled digital twin maintenancemodel is designed for production planning,which gives production instructions fromthe private industrial cloud server.To cope with the dynamic disturbances of a PMS,a big data-driven framework is proposed to control the three-level digital twin models,which contains indicator prediction,influence evaluation,and decisionmaking.Finally,a case study with a real chemical fiber system is introduced to illustrate the effectiveness of the digital twin model with edge-fog-cloud computing for the systematic PHM of PMSs.The result demonstrates that the three-leveled digital twin model for the systematic PHM in PMSs works well in the system’s respects.

Evaluation of new IPSS-Molecular model and comparison of different prognostic systems in patients with myelodysplastic syndrome

A risk-adapted treatment strategy is of crucial importance in patients with myelodysplastic syndromes(MDS).Previous risk prognostic scoring systems did not integrate molecular abnormalities.The new IPSS-Molecular(IPSS-M)model,combing genomic profiling with hematologic and cytogenetic parameters,was recently developed to evaluate the associations with leukemia-free survival(LFS),leukemic transformation,and overall survival(OS).However,it has not yet been widely validated in clinics.This study aims to further validate the prognostic power of IPSS-M based on real-world data and to compare the prognostic value of different scoring systems in patients with MDS.IPSS-M Web calculator was used to calculate a tailored IPSS-M score of the enrolled patient(N=255),and the risk category was defined correspondingly.We next compared the IPSS-M prognostic power to that of IPSS,IPSS-R,and WPSS.We found that IPSS-M risk classification was statistically significant for 3-year OS and LFS.Compared with other tools,IPSS-M was superior in sensitivity and accuracy for 3-year OS and LFS.The mapping C-index between IPSS-R and IPSS-M categories resulted in improved discrimination across the OS,but not LFS and leukemic transformation.The result of different treatment options indicated that allogeneic hematopoietic stem cell transplantation(allo-HSCT)can result in a better OS than those without allo-HSCT.In conclusion,IPSS-M was a valuable tool for risk stratification compared with other risk prognostic scoring systems.However,more studies should be conducted to explore the appropriate treatment options for different groups stratified by IPSS-M.

Prognostic and diagnostic scoring models in acute alcoholassociated hepatitis:A review comparing the performance of different scoring systems

Alcohol-associated hepatitis(AAH)is a severe form of liver disease caused by alcohol consumption.In the absence of confounding factors,clinical features and laboratory markers are sufficient to diagnose AAH,rule out alternative causes of liver injury and assess disease severity.Due to the elevated mortality of AAH,assessing the prognosis is a radical step in management.The Maddrey discriminant function(MDF)is the first established clinical prognostic score for AAH and was commonly used in the earliest AAH clinical trials.A MDF>32 indicates a poor prognosis and a potential benefit of initiating corticosteroids.The model for end stage liver disease(MELD)score has been studied for AAH prognostication and new evidence suggests MELD may predict mortality more accurately than MDF.The Lille score is usually combined to MDF or MELD score after corticosteroid initiation and offers the advantage of assessing response to treatment a 4-7 d into the course.Other commonly used scores include the Glasgow Alcoholic Hepatitis Score and the Age Bilirubin international normalized ratio Creatinine model.Clinical AAH correlate adequately with histologic severity scores and leave little indication for liver biopsy in assessing AAH prognosis.AAH presenting as acute on chronic liver failure(ACLF)is so far prognosticated with ACLF-specific scoring systems.New artificial intelligence-generated prognostic models have emerged and are being studied for use in AAH.Acute kidney injury(AKI)is one possible complication of AAH and is significantly associated with increased AAH mortality.Predicting AKI and alcohol relapse are important steps in the management of AAH.The aim of this review is to discuss the performance and limitations of different scoring models for AAH mortality,emphasize the most useful tools in prognostication and review predictors of recurrence.

Virtual sample generation for model-based prognostics and health management of on-board high-speed train control system

In view of class imbalance in data-driven modeling for Prognostics and Health Management(PHM),existing classification methods may fail in generating effective fault prediction models for the on-board high-speed train control equipment.A virtual sample generation solution based on Generative Adversarial Network(GAN)is proposed to overcome this shortcoming.Aiming at augmenting the sample classes with the imbalanced data problem,the GAN-based virtual sample generation strategy is embedded into the establishment of fault prediction models.Under the PHM framework of the on-board train control system,the virtual sample generation principle and the detailed procedures are presented.With the enhanced class-balancing mechanism and the designed sample augmentation logic,the PHM scheme of the on-board train control equipment has powerful data condition adaptability and can effectively predict the fault probability and life cycle status.Practical data from a specific type of on-board train control system is employed for the validation of the presented solution.The comparative results indicate that GAN-based sample augmentation is capable of achieving a desirable sample balancing level and enhancing the performance of correspondingly derived fault prediction models for the Condition-based Maintenance(CBM)operations.

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.

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 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.

Preoperative controlling nutritional status as an optimal prognostic nutritional index to predict the outcome for colorectal cancer

BACKGROUND The controlling nutritional status(CONUT)score effectively reflects a patient’s nutritional status,which is closely related to cancer prognosis.This study invest-igated the relationship between the CONUT score and prognosis after radical surgery for colorectal cancer,and compared the predictive ability of the CONUT score with other indexes.AIM To analyze the predictive performance of the CONUT score for the survival rate of colorectal cancer patients who underwent potentially curative resection.METHODS This retrospective analysis included 217 patients with newly diagnosed colorectal.The CONUT score was calculated based on the serum albumin level,total lymphocyte count,and total cholesterol level.The cutoff value of the CONUT score for predicting prognosis was 4 according to the Youden Index by the receiver operating characteristic curve.The associations between the CONUT score and the prognosis were performed using Kaplan-Meier curves and Cox regression analysis.RESULTS Using the cutoff value of the CONUT score,patients were stratified into CONUT low(n=189)and CONUT high groups(n=28).The CONUT high group had worse overall survival(OS)(P=0.013)and relapse-free survival(RFS)(P=0.015).The predictive performance of CONUT was superior to the modified Glasgow prognostic score,the prognostic nutritional index,and the neutrophil-to-lymphocyte ratio.Meanwhile,the predictive performances of CONUT+tumor node metastasis(TNM)stage for 3-year OS[area under the receiver operating characteristics curve(AUC)=0.803]and 3-year RFS(AUC=0.752)were no less than skeletal muscle mass index(SMI)+TNM stage.The CONUT score was negatively correlated with SMI(P<0.01).CONCLUSION As a nutritional indicator,the CONUT score could predict long-term outcomes after radical surgery for colorectal cancer,and its predictive ability was superior to other indexes.The correlation between the CONUT score and skeletal muscle may be one of the factors that play a predictive role.

Prognostic analysis of related factors of adverse reactions to immunotherapy in advanced gastric cancer and establishment of a nomogram model

BACKGROUND Immunotherapy for advanced gastric cancer has attracted widespread attention in recent years.However,the adverse reactions of immunotherapy and its relationship with patient prognosis still need further study.In order to determine the association between adverse reaction factors and prognosis,the aim of this study was to conduct a systematic prognostic analysis.By comprehensively evaluating the clinical data of patients with advanced gastric cancer treated by immunotherapy,a nomogram model will be established to predict the survival status of patients more accurately.AIM To explore the characteristics and predictors of immune-related adverse reactions(irAEs)in advanced gastric cancer patients receiving immunotherapy with programmed death protein-1(PD-1)inhibitors and to analyze the correlation between irAEs and patient prognosis.METHODS A total of 140 patients with advanced gastric cancer who were treated with PD-1 inhibitors in our hospital from June 2021 to October 2023 were selected.Patients were divided into the irAEs group and the non-irAEs group according to whether or not irAEs occurred.Clinical features,manifestations,and prognosis of irAEs in the two groups were collected and analyzed.A multivariate logistic regression model was used to analyze the related factors affecting the occurrence of irAEs,and the prediction model of irAEs was established.The receiver operating characteristic(ROC)curve was used to evaluate the ability of different indicators to predict irAEs.A Kaplan-Meier survival curve was used to analyze the correlation between irAEs and prognosis.The Cox proportional risk model was used to analyze the related factors affecting the prognosis of patients.RESULTS A total of 132 patients were followed up,of whom 63(47.7%)developed irAEs.We looked at the two groups’clinical features and found that the two groups were statistically different in age≥65 years,Ki-67 index,white blood cell count,neutrophil count,and regulatory T cell(Treg)count(all P<0.05).Multivariate logistic regression analysis showed that Treg count was a protective factor affecting irAEs occurrence(P=0.030).The ROC curve indicated that Treg+Ki-67+age(≥65 years)combined could predict irAEs well(area under the curve=0.753,95%confidence interval:0.623-0.848,P=0.001).Results of the Kaplan-Meier survival curve showed that progressionfree survival(PFS)was longer in the irAEs group than in the non-irAEs group(P=0.001).Cox proportional hazard regression analysis suggested that the occurrence of irAEs was an independent factor for PFS(P=0.006).CONCLUSION The number of Treg cells is a separate factor that affects irAEs in advanced gastric cancer patients receiving PD-1 inhibitor immunotherapy.irAEs can affect the patients’PFS and result in longer PFS.Treg+Ki-67+age(≥65 years old)combined can better predict the occurrence of adverse reactions.

Systematic analysis of DNA polymerases as therapeutic targets in pan-cancers

Introduction:DNA polymerases are crucial for maintaining genome stability and influencing tumorigenesis.However,the clinical implications of DNA polymerases in tumorigenesis and their potential as anti-cancer therapy targets are not well understood.Methods:We conducted a systematic analysis using TCGA Pan-Cancer Atlas data and Gene Set Cancer Analysis results to examine the expression profiles of 15 DNA polymerases(POLYs)and their clinical correlations.We also evaluated the prognostic value of POLYs by analyzing their expression levels in relation to overall survival time(OS)using Kaplan-Meier survival curves.Additionally,we investigated the correlations between POLY expression and immune cells,DNA damage repair(DDR)pathways,and ubiquitination.Drug sensitivity analysis was performed to assess the relationship between POLY expression and drug response.Results:Our analysis revealed that 14 out of 15 POLYs exhibited significantly distinct expression patterns between tumor and normal samples across most cancer types,except for DNA nucleotidylexotransferase(DNTT).Specifically,POLD1 and POLE showed elevated expression in almost all cancers,while POLQ exhibited high expression levels in all cancer types.Some POLYs showed heightened expression in specific cancer subtypes,while others exhibited low expression.Kaplan-Meier survival curves demonstrated significant prognostic value of POLYs in multiple cancers,including PAAD,KIRC,and ACC.Cox analysis further validated these findings.Alteration patterns of POLYs varied significantly among different cancer types and were associated with poorer survival outcomes.Significant correlations were observed between the expression of POLY members and immune cells,DDR pathways,and ubiquitination.Drug sensitivity analysis indicated an inverse relationship between POLY expression and drug response.Conclusion:Our comprehensive study highlights the significant role of POLYs in cancer development and identifies them as promising prognostic and immunological biomarkers for various cancer types.Additionally,targeting POLYs therapeutically holds promise for tumor immunotherapy.

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.

Novel prognostic factors after radical resection of hepatocellular carcinoma: Updating an old issue

In this editorial,I comment on the article by Li et al published in the recent issue of the World Journal of Gastrointestinal Surgery in 2023,investigating the role of some novel prognostic factors for early survival after radical resection of liver cancer.Liver cancer is an important burden among Asian and Western popu-lations,despite recent advances in both medicine(from virus eradication to systemic target therapies)and surgery.However,survival after proven radical surgery remains poor,with recurrences being the rule.Many prognostic scores have been developed and validated to select those patients who will best benefit from radical liver surgery,although the final general and oncological outcomes continue to be highly jeopardized.Unfortunately,no single biomarker can resolve all these issues for hepatocellular carcinoma,and it remains to be proven whether some of them main-tain predictive power in the long-term follow-up.In the ongoing era of“preci-sion”medicine,the novel prognostic markers,including immune inflammatory and nutritional indexes could be of great help in better stratify surgical candi-dates.

Preoperative prognostic nutritional index predicts long-term outcomes of patients with ampullary adenocarcinoma after curative pancreatoduodenectomy

BACKGROUND The prognostic nutritional index(PNI),a marker of immune-nutrition balance,has predictive value for the survival and prognosis of patients with various cancers.AIM To explore the clinical significance of the preoperative PNI on the prognosis of ampullary adenocarcinoma(AC)patients who underwent curative pancreaticoduodenectomy.METHODS The data concerning 233 patients diagnosed with ACs were extracted and analyzed at our institution from January 1998 to December 2020.All patients were categorized into low and high PNI groups based on the cutoff value determined by receiver operating characteristic curve analysis.We compared disease-free survival(DFS)and overall survival(OS)between these groups and assessed prognostic factors through univariate and multivariate analyses.RESULTS The optimal cutoff value for the PNI was established at 45.3.Patients with a PNI≥45.3 were categorized into the PNI-high group,while those with a PNI<45.3 were assigned to the PNI-low group.Patients within the PNI-low group tended to be of advanced age and exhibited higher levels of aspartate transaminase and total bilirubin and a lower creatinine level than were those in the PNI-high group.The 5-year OS rates for patients with a PNI≥45.3 and a PNI<45.3 were 61.8%and 43.4%,respectively,while the 5-year DFS rates were 53.5%and 38.3%,respectively.Patients in the PNI-low group had shorter OS(P=0.006)and DFS(P=0.012).In addition,multivariate analysis revealed that the PNI,pathological T stage and pathological N stage were found to be independent prognostic factors for both OS and DFS.CONCLUSION The PNI is a straightforward and valuable marker for predicting long-term survival after pancreatoduodenectomy.The PNI should be incorporated into the standard assessment of patients with AC.