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

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World Journal of Gastroenterology 2024年第9期30卷 1177-1188页

作者： Song-Man Yu Hai Li Guo-Hong Deng Xian-Bo Wang Xin Zheng Jin-Jun Chen Zhong-Ji Meng Yu-Bao Zheng Yan-Hang Gao Zhi-Ping Qian Feng Liu Xiao-Bo Lu Yu Shi Jia Shang Ruo-Chan Chen Yan Huang Department of Infectious Diseases Xiangya HospitalCentral South UniversityChangsha 410000Hunan ProvinceChina Department of Gastroenterology Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China Department of Infectious Diseases Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Center of Integrative Medicine Beijing Ditan HospitalCapital Medical UniversityBeijing 100020China Department of Infectious Diseases Institute of Infection and ImmunologyUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430020Hubei ProvinceChina Department of Infectious Diseases Nanfang HospitalSouthern Medical UniversityGuangzhou 510515Guangdong ProvinceChina Department of Infectious Disease Taihe HospitalHubei University of MedicineShiyan 442009Hubei ProvinceChina Department of Infectious Diseases The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630Guangdong ProvinceChina Department of Hepatology The First Hospital of Jilin UniversityChangchun 130021Jilin ProvinceChina Department of Liver Intensive Care Unit Shanghai Public Health Clinical CentreFudan UniversityShanghai 200093China Tianjin Institute of Hepatology Nankai University Second People's HospitalTianjin 300192China Infectious Disease Center The First Affiliated Hospital of Xinjiang Medical UniversityUrumqi 830054Xinjiang Uygur Autonomous RegionChina The State Key Laboratory for Diagnosis and Treatment of Infectious Diseases The First Affiliated Hospital of School of MedicineZhejiang UniversityHangzhou 310003Zhejiang ProvineChina Department of Infectious Diseases Henan Provincial People's HospitalZhengzhou 463599Henan ProvineChina Department of Infectious Diseases Hunan Key Laboratory of Viral HepatitisXiangya HospitalCentral South UniversityChangsha 110051Hunan ProvineChina

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.

关键词： Soluble triggering receptor expressed on myeloid cell-1 Acute decompensation Cirrhosis Acute-on-chronic liver failure prognostic biomarker

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Comprehensive proteomic signature and identification of CDKN2A as a promising prognostic biomarker and therapeutic target of colorectal cancer

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World Journal of Clinical Cases 2022年第22期10卷 7686-7697页

作者： Qian-Qian Wang Yuan-Chen Zhou Yu-Jia Zhou Ge Geng Qin Teng-Fei Yin Dong-Yan Zhao Chang Tan Shu-Kun Yao Graduate School Peking University China-Japan Friendship School of Clinical MedicineBeijing 10029China Graduate School Peking Union Medical College and Chinese Academy of Medical SciencesBeijing 100730China of Gastroenterology China-Japan Friendship HospitalBeijing 100029China Graduate School Peking University China-Japan Friendship School of Clinical MedicineBeijing 100029China

BACKGROUND The carcinogenesis of colorectal cancer(CRC)involves many different molecules and multiple pathways,and the specific mechanism has not been elucidated until now.Existing studies on the proteomic signature profiles of CRC are relatively limited.Therefore,we herein aimed to provide a more comprehensive proteomic signature profile and discover new prognostic markers and therapeutic targets by performing proteomic analysis of CRC and paired normal tissues.AIM To investigate the proteomic signature and identify novel protein prognostic biomarkers of CRC.METHODS Cancer tissues and paired normal tissues were collected from 48 patients who underwent surgical removal at the China-Japan Friendship Hospital from January 2020 to June 2021.Data independent acquisition(DIA)quantitative proteomic analysis was performed using high-performance liquid chromatography–mass spectrometry/mass spectrometry(nano-UHPLC–MS/MS)to identify differen tially expressed proteins,among which those with a P adj value(t test,BH correction)2 were identified as potential markers.Differentially expressed proteins were selected by bioinformatics analysis and validated by immunohistochemical tissue microarrays,and their association with prognosis was further analyzed with the Gene Expression Profiling Interactive Analysis database to identify prognostic protein biomarkers of CRC.RESULTS Significantly differential protein expression was observed between cancer tissues and normal tissues.Compared with normal tissues,1115 proteins were upregulated and 705 proteins were downregulated in CRC based on P adj2,and bioinformatics analysis revealed that the differentially expressed proteins were involved in multiple biological processes associated with tumorigenesis,including ribosome biogenesis in eukaryotes,focal adhesion,extracellular matrix-receptor interactions and other tumor metabolism processes.Moreover,cyclin-dependent kinase inhibitor 2A(CDKN2A)expression was markedly upregulated i

关键词： Colorectal cancer Proteomic analysis Cyclin-dependent kinase inhibitor 2A prognostic biomarker Therapeutic target Precision treatment

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Long non-coding RNA MALAT1 in hematological malignancies and its clinical applications

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中华医学杂志(英文版) 2024年第10期137卷 1151-1159页

作者： Zhang Chunlan Qin Yun Wu Yu Xu Heng Shu Yang Department of Hematology West China Hospital Sichuan University Chengdu Sichuan China Department of Radiology West China Hospital Sichuan University Chengdu Sichuan China Department of Laboratory Medicine/Research Center of Clinical Laboratory Medicine West China Hospital Sichuan University Chengdu Sichuan China Department of Biotherapy State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu Sichuan China Institute of General Surgery West China Hospital Sichuan University Chengdu Sichuan China Department of General Surgery Gastric Cancer Center and Laboratory of Gastric Cancer West China Hospital Sichuan University Chengdu Sichuan China

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a well-established oncogenic long non-coding RNA, the higher expression of which is strongly correlated with cancer events such as tumorigenesis, progression, metastasis, drug resistance, and treatment outcome in solid cancers. Recently, a series of studies has highlighted its potential role in hematological malignancies in terms of these events. Similar to solid cancers,MALAT1 can regulate various target genes via sponging and epigenetic mechanisms, but the miRNAs sponged byMALAT1 differ from those identified in solid cancers. In this review, we systematically describe the role and underlying mechanisms ofMALAT1 in multiple types of hematological malignancies, including regulation of cell proliferation, metastasis, stress response, and glycolysis. Clinically,MALAT1 expression is related to poor treatment outcome and drug resistance, therefore exhibiting potential prognostic value in multiple myeloma, lymphoma, and leukemia. Finally, we discuss the evaluation ofMALAT1 as a novel therapeutic target against cancer in preclinical studies.

关键词： Long non-coding RNA MALAT1 Hematological malignancies Tumorigenesis Metastasis Drug resistance prognostic biomarker

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Red cell distribution width/platelet ratio estimates the 3-year risk of decompensation in Metabolic Dysfunction-Associated Steatotic Liver Disease-induced cirrhosis

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World Journal of Gastroenterology 2024年第7期30卷 685-704页

作者： Marcello Dallio Mario Romeo Paolo Vaia Salvatore Auletta Simone Mammone Marina Cipullo Luigi Sapio Angela Ragone Marco Niosi Silvio Naviglio Alessandro Federico Department of Precision Medicine Hepatogastroenterology DivisionUniversity of Campania Luigi VanvitelliNaples 80138Italy Department of Precision Medicine Clinical Biochemistry DivisionUniversity of Campania Luigi VanvitelliNaples 80138Italy

BACKGROUND For compensated advanced chronic liver disease(cACLD)patients,the first decompensation represents a dramatically worsening prognostic event.Based on the first decompensation event(DE),the transition to decompensated advanced chronic liver disease(dACLD)can occur through two modalities referred to as acute decompensation(AD)and non-AD(NAD),respectively.Clinically Significant Portal Hypertension(CSPH)is considered the strongest predictor of decompensation in these patients.However,due to its invasiveness and costs,CSPH is almost never evaluated in clinical practice.Therefore,recognizing noninvasively predicting tools still have more appeal across healthcare systems.The red cell distribution width to platelet ratio(RPR)has been reported to be an indicator of hepatic fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD).However,its predictive role for the decompensation has never been explored.AIM In this observational study,we investigated the clinical usage of RPR in predicting DEs in MASLD-related cACLD patients.METHODS Fourty controls and 150 MASLD-cACLD patients were consecutively enrolled and followed up(FUP)semiannually for 3 years.At baseline,biochemical,clinical,and Liver Stiffness Measurement(LSM),Child-Pugh(CP),Model for End-Stage Liver Disease(MELD),aspartate aminotransferase/platelet count ratio index(APRI),Fibrosis-4(FIB-4),Albumin-Bilirubin(ALBI),ALBI-FIB-4,and RPR were collected.During FUP,DEs(timing and modaities)were recorded.CSPH was assessed at the baseline and on DE occurrence according to the available Clinical Practice Guidelines.RESULTS Of 150 MASLD-related cACLD patients,43(28.6%)progressed to dACLD at a median time of 28.9 months(29 NAD and 14 AD).Baseline RPR values were significantly higher in cACLD in comparison to controls,as well as MELD,CP,APRI,FIB-4,ALBI,ALBI-FIB-4,and LSM in dACLD-progressing compared to cACLD individuals[all P0.472 and>0.894 as the best

关键词： Liver cirrhosis Red blood cell distribution width Red blood cell distribution width to platelet ratio Translational Medicine prognostic biomarker

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A pan-cancer analysis identifies SOAT1 as an immunological and prognostic biomarker

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Oncology Research 2023年第2期31卷 193-205页

作者： YANGQING HUANG XINLAN ZHOU XIUFEN LI DAN HUANG ZHONG FANG RONGRONG DING Department of Hepatobiliary Medicine Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina Department of Hepatobiliary Surgery Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina Liver Cancer Institute of Zhongshan Hospital and Key Laboratory of Carcinogenesis and Cancer Invasion(Ministry of Education) School of Basic Medical SciencesFudan UniversityShanghaiChina

Sterol o-acyltransferase1(SOAT1)is an enzyme that regulates lipid metabolism.Nevertheless,the predictive value of SOAT1 regarding immune responses in cancer is not fully understood.Herein,we aimed to expound the predictive value and the potential biological functions of SOAT1 in pan-cancer.Raw data related to SOAT1 expression in 33 different types of cancer were acquired from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases.SOAT1 expression was significantly increased in most cancers and showed a distinct correlation with prognosis.This enhanced expression of the SOAT1 gene was confirmed by evaluating SOAT1 protein expression using tissue microarrays.In addition,we found significant positive associations between SOAT1 expression levels and infiltrating immune cells,including T cells,neutrophils,and macrophages.Moreover,the co-expression analysis between SOAT1 and immune genes showed that many immune-related genes were increased with enhanced SOAT1 expression.A gene set enrichment analysis(GSEA)revealed that the expression of SOAT1 correlated with the tumor microenvironment,adaptive immune response,interferon signaling,and cytokine signaling.These findings indicate that SOAT1 is a potential candidate marker for predicting prognosis and a promising target for tumor immunotherapy in cancers.

关键词： SOAT1 Pan-cancer Immune infiltration prognostic biomarker Tumor microenvironment

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MUTYH is a potential prognostic biomarker and correlates with immune infiltrates in hepatocellular carcinoma

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Liver Research 2022年第4期6卷 258-268页

作者： Fan Yang Qinghai Lian Beibei Ni Xiusheng Qiu Yizhan He Xiaoguang Zou Fangping He Wenjie Chen Biotherapy Center The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Department of Infectious Diseases The First People's Hospital of KashiKashiXinjiangChina Xinjiang Medical University UrumqiXinjiangChina Cell-gene Therapy Translational Medicine Research Center The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Department of Hepatobiliary and Pancreatic Surgery The Eighth Affiliated Hospital of Sun Yat-sen UniversityShenzhenGuangdongChina

Background:Hepatocellular carcinoma(HCC)is a leading cause of cancer-related death worldwide.The development of biomarkers for early detection and monitoring of HCC has not shown significant prog-ress.Meanwhile,the second adenomatous polyposis-related gene,MUTYH,which encodes a DNA gly-cosylase,has been observed in its contribution to oxidative DNA damage repair.Abnormal expression of MUTYH can reduce cell survival rate.Therefore,this study investigated the usefulness of MUTYH in diagnosing and prognosis HCC.Materials and methods:Using The Cancer Genome Atlas(TCGA)data,we analyzed the prognostic value of MUTYH in HCC.We used logistic regression,Wilcoxon signed-rank test,and KruskaleWallis test to examine MUTYH expression concerning clinical-pathologic characteristics.Univariate and multivariate Cox regression methods and Kaplan-Meier analysis were applied to determine the related prognostic factors of HCC.The enrichment analysis(GSEA)was used to determine the critical pathways associated with MUTYH.The single-sample gene set enrichment analysis(ssGSEA)was conducted to examine the correlation between MUTYH expression and cancer immune infiltration.Results:The higher expression of MUTYH in HCC patients was associated with a poorer overall survival rate and a shorter disease-specific survival rate.The Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis showed that all differentially expressed genes(DEGs)between the high and low expression levels of MUTYH significantly enriched in the trace ligand-receptor interaction,cell cycle,oocyte meiosis,gap junction,and DNA replication.Group analysis revealed the signals of their open access.The neuron system,M phase,DNA repair,Rho GTPase effector,and cell cycle checkpoints were significantly enriched.ssGSEA showed a positive correlation between MUTYH expression and the infiltration levels of Th2 cells,NK cells,and T helper cells.Moreover,a negative correlation was found between MUTYH expression and the infiltration levels of dendritic cells(DCs)and cytotoxic cells.Conclusio

关键词： MUTYH Hepatocellular carcinoma(HCC) Bioinformatics prognostic biomarker Immune infiltrates

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

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BIOCELL 2024年第1期48卷 123-138页

作者： ZHENHUA LI HUILAI LV FAN ZHANG ZIMING ZHU QIANG GUO MINGBO WANG CHAO HUANG LIJUAN CHEN WENPAN ZHANG YUN LI ZIQIANG TIAN Department of Thoracic Surgery Fourth Hospital of Hebei Medical UniversityShijiazhuang050011China Department of Thoracic Surgery The First Hospital of XingtaiXingtai054001China Department of Thoracic Surgery Affiliated Hospital of Hebei UniversityBaoding050017China Shanghai OrigiMed Co. Ltd.Shanghai200000China Department of Thoracic Surgery The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China

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 type

关键词： DNA polymerases(POLYs) prognostic biomarker The Cancer Genome Atlas(TCGA) Ubiquitination network

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The prognostic and immunological impacts of DCX expression:a pan-cancer analysis

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Cancer Advances 2024年第14期7卷 1-8页

作者： Xin Li Wan-Rong Li Hao Jin Tianjin Cancer Hospital Airport Hospital Tianjin 300060China Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin’s Clinical Research Center for CancerTianjin 300060China.

Background:Doublecortin(DCX),a microtubule-associated protein,is best known for its critical role in neuronal migration during neural development,where it stabilizes microtubules and guides neurons to their proper positions.Recently,DCX has been implicated in various cancer processes,suggesting it may influence tumor progression and the tumor microenvironment.Emerging evidence indicates that DCX can modulate cell migration,invasion,and interaction with immune cells,making it a potential player in oncogenesis.However,the role of DCX across different cancer types and its potential as a prognostic biomarker remain underexplored,necessitating a comprehensive analysis.Methods:We utilized The Cancer Genome Atlas to extract data on DCX expression in tumor and adjacent normal tissues across diverse cancer types.Differential expression analysis was conducted using differential expression sequencing 2.Survival analysis was performed with Kaplan-Meier estimates and Cox proportional hazards models.Correlations between DCX expression and tumor mutational burden,microsatellite instability,and immune infiltration were examined using Spearman’s correlation.Results:DCX showed variable expression across cancer types,with significant overexpression in certain tumors such as liver and lung cancer and downexpression in others like breast cancer.High DCX expression was correlated with poor prognosis in adrenocortical carcinoma but with better outcomes in low-grade glioma.Additionally,DCX expression was significantly associated with various immune markers and chemokines,suggesting a role in modulating the immune microenvironment.Conclusion:Our findings highlight the complex role of DCX in cancer,underlining its potential as a prognostic marker and its involvement in immune-related pathways.Targeting DCX could represent a novel approach to modulating tumor behavior and enhancing immune response in cancer therapy.

关键词： pan-cancer analysis tumor microenvironment prognostic biomarker immune infiltration chemokine signaling cancer genomics

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Recognition of prognostic biomarker and its association with immune infiltrates in breast cancer associated with inflammation

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Precision Medicine Research 2022年第1期4卷 1-13页

作者： Shun Wang Zhi Li Hua Zhang Qun Wang Department of General Surgery Taihe HospitalHubei University of MedicineShiyan 442000China Shiyan Taihe Hospital Graduate Training Base Jinzhou Medical UniversityJinzhou 121001China

Objective:To identify prognostic biomarkers in breast cancer(BRCA)associated with inflammation.Materials andmethods:WGCNA was used to identify prognostic biomarkers in BRCA based on TCGA-BRCA and GSE70947 datasets.GO and KEGG exploration was made to analyze the specific mechanisms of interest genes.Results:There were 9 modules in TCGA-BRCA and 19 modules in the GSE70947 constructed and 639 overlapping genes extracted.There were ten genes recognized as hub genes,SAA1 and CXCL2 were identified as key genes.Furthermore,we found that SAA1 and CXCL2 were positively related to the levels of tumor-infiltrating immune cells in BRCA with TIMER.Conclusions:SAA1 and CXCL2 is highly correlated with BRCA and its prognosis was greatly related to TIICs.

关键词： breast cancer(BRCA) inflammation prognostic biomarker tumor-infiltrating immune cells

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m7G Methylation-Related Gene NUDT10 as novel prognostic biomarker and its ceRNA regulatory network in colorectal cancer

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Medical Data Mining 2023年第2期6卷 7-20页

作者： Yu-Jian Li Xuan Kan Department of Pediatrics General Hospital of Tianjin Medical UniversityTianjin 300052China

Background:Colorectal cancer(CRC)is a life-threatening malignant disease of the digestive system,which is still a leading cause of cancer death worldwide.RNA methylation,a fundamental process in epigenetic regulation,also plays an important role in tumor development.Nevertheless,the functional mechanisms of 7-methylguanosine(m7G)methylation-related gene in CRC are unclear.Methods:The differential expression of m7G methylation-related gene between CRC tissues and normal tissues in UCSC XENA,TCGA and GTEx was verified using R.Cox regression,Nomogram were used to construct corresponding prognostic models of CRC.Kaplan-Meier analysis,receiver operating characteristic curve analysis,clinical correlation analysis and enrichment analysis were used to further investigate the correlation and functional mechanisms of m7G methylation-related gene with CRC.Immuno-infiltration was used to verify the relationship between nudix hydroxylase 10(NUDT10)and immune cells,while methylation analysis was used to study the promoter methylation of NUDT10.Immunohistochemistry was used to analyze the protein expression between CRC tissues and normal tissues.The ceRNA regulatory network was used to identify the mRNA-miRNA-lncRNA regulatory axis.Results:The m7G methylation-related gene NUDT10 was lowly expressed in CRC.Cox regression,Nomogram and calibration curve finally identified NUDT10 as the novel prognostic biomarker of CRC and constructed the corresponding prognostic models.The results of immunohistochemistry showed that the protein expression levels of NUDT10 differed between CRC tissues and normal tissues.In addition,NUDT10 had predictive power for CRC and the expression of NUDT10 in CRC was closely associated with immune infiltration.Gene Ontology,Kyoto Encyclopedia of Genes and Genomes and Gene Set Enrichment Analysis revealed that biological functions such as the regulation of angiogenesis,muscle contraction,transporter complex and gated channel activity,pathways such as heme metabolism,hypoxia,cholinergic synapse,apical junction

关键词： 7-methylguanosine methylation colorectal cancer ceRNA prognostic biomarker immune infiltration

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