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Transcriptome sequencing reveals novel biomarkers and immune cell infiltration in esophageal tumorigenesis

World Journal of Gastrointestinal Oncology 2024年第4期16卷 1500-1513页

作者： Jian-Rong Sun Dong-Mei Chen Rong Huang Rui-Tao Wang Li-Qun Jia School of Clinical Medicine Beijing University of Chinese MedicineBeijing 100029China Integrated Chinese and Western Medicine Oncology China-Japan Friendship HospitalBeijing 100029China

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most common malignancies worldwide,and its development comprises a multistep process from intraepithelial neoplasia(IN)to carcinoma(CA).However,the critical regulators and underlying molecular mechanisms remain largely *** To explore the genes and infiltrating immune cells in the microenvironment that are associated with the multistage progression of ESCC to facilitate diagnosis and early *** A mouse model mimicking the multistage development of ESCC was established by providing warter containing 4-nitroquinoline 1-oxide(4NQO)to C57BL/6 ***,we established a control group without 4NQO treatment of ***,transcriptome sequencing was performed for esophageal tissues from patients with different pathological statuses,including low-grade IN(LGIN),high-grade IN(HGIN),and CA,and controlled normal tissue(NOR)*** expressed genes(DEGs)were identified in the LGIN,HGIN,and CA groups,and the biological functions of the DEGs were analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment *** CIBERSORT algorithm was used to detect the pattern of immune cell ***(IHC)was also conducted to validate our ***,the Luminex multiplex cytokine analysis was utilized to measure the serum cytokine levels in the *** Compared with those in the NOR group,a total of 681541,and 840 DEGs were obtained in the LGIN,HGIN,and CA groups,*** the intersection of the three sets of DEGs,we identified 86 genes as key genes involved in the development of *** analysis revealed that these genes were enriched mainly in the keratinization,epidermal cell differentiation,and interleukin(IL)-17 signaling *** analysis revealed that,compared with those in the NOR group,M0 and M1 macrophages in the 4NQO group showed stronger infiltration,which was validated by *** cytok

关键词： Esophageal squamous cell carcinoma Intraepithelial neoplasia Tumorigenesis Transcriptome sequencing Biomarkers immune cell infiltration 4-nitroquinoline 1-oxid

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Analysis and validation of diagnostic biomarkers and immune cell infiltration characteristics in pediatric sepsis by integrating bioinformatics and machine learning

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World Journal of Pediatrics 2023年第11期19卷 1094-1103页

作者： Wen‑Yuan Zhang Zhong‑Hua Chen Xiao‑Xia An Hui Li Hua‑Lin Zhang Shui‑Jing Wu Yu‑Qian Guo Kai Zhang Cong‑Li Zeng Xiang‑Ming Fang Department of Anesthesiology and Intensive Care School of MedicineThe First Affiliated HospitalZhejiang UniversityQingChun Road 79Hangzhou 310003China Department of Anesthesiology Shaoxing People’s Hospital(Shaoxing HospitalZhejiang University School of Medicine)Shaoxing 312000China Department of Anesthesiology Vagelos College of Physicians and SurgeonsColumbia UniversityNew YorkNYUSA

Background Pediatric sepsis is a complicated condition characterized by life-threatening organ failure resulting from a dysregulated host response to infection in *** is associated with high rates of morbidity and mortality,and rapid detection and administration of antimicrobials have been *** objective of this study was to evaluate the diagnostic biomarkers of pediatric sepsis and the function of immune cell infiltration in the development of this *** Three gene expression datasets were available from the Gene Expression Omnibus ***,the differentially expressed genes(DEGs)were found with the use of the R program,and then gene set enrichment analysis was carried ***,the DEGs were combined with the major module genes chosen using the weighted gene co-expression *** hub genes were identified by the use of three machine-learning algorithms:random forest,support vector machine-recursive feature elimination,and least absolute shrinkage and selection *** receiver operating characteristic curve and nomogram model were used to verify the discrimination and efficacy of the hub *** addition,the inflammatory and immune status of pediatric sepsis was assessed using cell-type identification by estimating relative subsets of RNA transcripts(CIBERSORT).The relationship between the diagnostic markers and infiltrating immune cells was further *** Overall,after overlapping key module genes and DEGs,we detected 402 overlapping *** pediatric sepsis diagnostic indicators,CYSTM1(AUC=0.988),MMP8(AUC=0.973),and CD177(AUC=0.986)were investigated and demonstrated statistically significant differences(Pimmune cell infiltration analysis,multiple immune cells may be involved in the development of pediatric ***,all diagnostic characteristics may correlate with immune cells to varying *** The candida

关键词： Paediatric sepsis Bioinformatics Machine-Learning Biomarkers immune cell infiltration

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Hub genes associated with immune cell infiltration in breast cancer, identified through bioinformatic analyses of multiple datasets

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Cancer Biology & Medicine 2022年第9期19卷 1352-1374页

作者： Huanyu Zhao Ruoyu Dang Yipan Zhu Baijian Qu Yasra Sayyed Ying Wen Xicheng Liu Jianping Lin Luyuan Li State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy Tianjin Key Laboratory of Molecular Drug ResearchNankai UniversityTianjin 300350China Department of Physiology and Pathophysiology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China

Objective:The aim of this study was to identify hub genes associated with immune cell infiltration in breast cancer through bioinformatic analyses of multiple ***:Nonparametric(NOISeq)and robust rank aggregation-ranked parametric(EdgeR)methods were used to assess robust differentially expressed genes across multiple ***-protein interaction network,GO,KEGG enrichment,and subnetwork analyses were performed to identify immune-associated hub genes in breast *** cell infiltration was evaluated with the CIBERSORT,Xcell,and TIMER *** association between the hub gene-based risk signature and survival was determined through Kaplan–Meier survival analysis,multivariate Cox analysis,and a nomogram with external ***:We identified 163 robust differentially expressed genes in breast cancer through applying both nonparametric and parametric methods to multiple GEO(n=2,212)and TCGA(n=1,045)*** bioinformatic analyses further identified 10 hub genes:CXCL10,CXCL9,CXCL11,SPP1,POSTN,MMP9,DPT,COL1A1,ADAMDEC1,and *** 10 hub-gene-based risk signature significantly correlated with the prognosis of patients with breast ***,these hub genes were strongly associated with the extent of infiltration of CD4+T cells,CD8+T cells,neutrophils,macrophages,and myeloid dendritic cells into breast ***:Integrated analyses of multiple databases led to the discovery of 10 robust hub genes that together may serve as a risk factor characteristic of the immune microenvironment in breast cancer.

关键词： Bioinformatics breast cancer multi-datasets analysis immune cell infiltration survival analysis

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Identification of immune cell infiltration landscape for predicting prognosis of colorectal cancer

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Gastroenterology Report 2023年第1期11卷 260-270页

作者： Xueqian Wu Jianxia Li Yuanzhe Zhang Yi Cheng Zehua Wu Weixiang Zhan Yanhong Deng Department of Medical Oncology The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongP.R.China Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease Guangdong Research Institute of GastroenterologyThe Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongP.R.China

Background:The tumor microenvironment plays an essential role in the therapeutic response to *** is necessary to identify immune cell infiltration(ICI)subtypes for evaluating prognosis and therapeutic *** study aimed to evaluate the ICI score as an effective prognostic biomarker for immune ***:The cell-type identification by estimating relative subsets of RNA transcripts and the estimation of stromal and immune cells in malignant tumors using expression methods were used to analyse ICI landscapes in 161 colorectal cancer(CRC)samples with patients’clinical and prognostic data,RNA sequencing data,and whole-exome sequencing data from the Sixth Affiliated Hospital,Sun Yat-sen University(Guangzhou,China).Statistical analysis and data processing were conducted to calculate ICI scores,and to analyse the prognosis of CRC patients with different ICI scores and other features.A similar analysis with RNA sequencing and clinical data of colon adenocarcinoma(COAD)samples from The Cancer Genome Atlas(TCGA)database was conducted to confirm the correctness of the ***:The high-ICI score group with a better prognosis(hazard ratio[HR],2.19;95%confidence interval[CI],1.03–4.64;logrank test,P=0.036)was characterized by the increased tumor mutational burden and interleukin-17(IL-17)signaling *** differences in the prognosis and the expression levels of immune checkpoints and chemokine marker genes were found between the two ICI score *** COAD samples from TCGA,the results also showed a significant difference in patients’prognosis between the two ICI score groups(HR,1.72;95%CI,1.00–2.96;log-rank test,P=0.047).Conclusions:Tumor heterogeneity induced differences in identifying ICI subtypes of CRC *** ICI score may serve as an effective biomarker for predicting prognosis,help identify new therapeutic markers for CRC,and develop novel effective immune checkpoint blockade therapies.

关键词： colorectal cancer prognosis immune cell infiltration ICI scores immunology tumor microenvironment

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Comprehensive analysis reveals hub genes associated with immune cell infiltration in allergic rhinitis

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2023年第4期9卷 340-351页

作者： Hui Li Shi-En Huang Cong-Li Geng Yu-Xiao Wu Mu-Han Shi Min Wang Department of Otorhinolaryngology Peking University People's HospitalBeijingChina Department of Rhinology The First Affliated Hospital of Zhengzhou UniversityZhengzhouChina

Objectives:Allergic rhinitis(AR)refers to a form of respiratory inflammation that mainly affects the sinonasal *** purpose of this study was to explore the level of immune cell infiltration and the pathogenesis of ***:We performed a comprehensive analysis of two gene expression profiles(GSE50223 and GSE50101,a total of 30 patients with AR and 31 healthy controls).CIBERSORT was used to evaluate the immune cell infiltration *** gene coexpression network analysis was applied to explore potential genes or gene modules related to immune status,and enrichment analyses including gene ontology,Kyoto Encyclopedia of Genes and Genomes,gene set enrichment analysis,and gene set variation analysis,were performed to analyze the potential mechanisms in AR.A protein–protein interaction network was constructed to investigate the hub genes,and consensus clustering was conducted to identify the molecular subtypes of ***:Compared to the healthy controls,patients with AR had high abundance levels and proportions of CD4+memory‐activated T *** hundred and eight immune‐related differentially expressed genes were *** analysis suggested that AR was mainly related to leukocyte cell‐cell adhesion,cytokine‐cytokine receptor interaction,T‐cell activation,and T‐cell receptor signaling *** hub genes,includingTYROBP,CSF1R,TLR8,FCER1G,SPI1,ITGAM,CYBB,FCGR2A,CCR1,andHCK,which were related to immune response,might be crucial to the pathogenesis of *** molecular subtypes with significantly different immune statuses were ***:This study improves our understanding of the molecular mechanisms in AR via comprehensive strategies and provides potential diagnostic biomarkers and therapeutic targets of AR.

关键词： allergic rhinitis CIBERSORT consensus cluster GSEA GSVA immune cell infiltration WGCNA

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Prognostic biomarkers and immune cell infiltration characteristics in small cell lung cancer

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Cancer Pathogenesis and Therapy 2023年第1期1卷 18-24页

作者： Jun Ni Xiaoyan Si Hanping Wang Xiaotong Zhang Li Zhang Department of Pulmonary and Critical Care Medicine Peking Union Medical College HospitalChinese Academy of Medical Science&Peking Union Medical CollegeBeijing 100730China

Background Small cell lung cancer(SCLC)is a highly malignant and aggressive neuroendocrine *** the rise of immunotherapy,it has provided a new direction for ***,due to the lack of prognostic biomarkers,the median overall survival of SCLC is still to be *** study aimed to explore novel biomarkers and tumor-infiltrating immune cell characteristics that may serve as potential diagnostic and prognostic markers in *** Gene expression profiles from patients with SCLC were downloaded from the Gene Expression Omnibus(GEO)database,and tumor microenvironment(TME)infiltration profile data were obtained using *** robust rank aggregation(RRA)method was utilized to integrate three SCLC microarray datasets downloaded from the GEO database and identify robust differentially expressed genes(DEGs)between normal and tumor tissue *** Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed to explore the functions of the robust ***,protein-protein interaction networks and key modules were constructed by Cytoscape,and hub genes were selected from the whole network using the plugin *** analysis of hub genes was performed by Kaplan-Meier plotter in 18 patients with extensive-stage *** A total of 312 robust DEGs,including 55 upregulated and 257 downregulated genes,were screened from 129 SCLC tissue samples and 44 normal tissue *** and KEGG enrichment analyses revealed that the robust DEGs were predominantly involved in human T-cell leukemia virus 1 infection,focal adhesion,complement and coagulation cascades,tumor necrosis factor(TNF)signaling pathway,and ECM-receptor interaction,which are closely associated with the development and progression of ***,three DEGs modules and six hub genes(ITGA10,DUSP12,PTGS2,FOS,TGFBR2,and ICAM1)were identified through screening with the Cytoscape plugins MCODE and cytoHubba,*** cell infiltra

关键词： Bioinformatics analysis Small cell lung cancer immune cell infiltration Tumor microenvironment Hub genes Protein interaction network Gene expression omnibus database

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Prognostic role of ring finger and WD repeat domain 3 and immune cell infiltration in hepatocellular carcinoma

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World Journal of Hepatology 2023年第1期15卷 116-122页

作者： Yan-Dong Miao Wu-Xia Quan Jiang-Tao Wang Jian Gan Xin Dong Fang Zhang Cancer Center Yantai Affiliated Hospital of Binzhou Medical UniversityYantai 264000Shandong ProvinceChina Department of Electrocardiogram Yantai Affiliated Hospital of Binzhou Medical UniversityYantai 264100Shandong ProvinceChina Department of Thyroid and Breast Surgery Yantai Affiliated Hospital of Binzhou Medical UniversityYantai 264000Shandong ProvinceChina Department of Gastroenterology Yantai Affiliated Hospital of Binzhou Medical UniversityYantai 264000Shandong ProvinceChina Second Department of Oncology Yantai Affiliated Hospital of Binzhou Medical UniversityYantai 264000Shandong ProvinceChina

We have found that the expression of ring finger and WD repeat domain 3(RFWD3)is significantly higher in unpaired and paired hepatocellular carcinoma(HCC)tissues than in normal ***,this expression has a significant correlation with the infiltration level of 14 immune cell types and when the detected RFWD3 expression levels were grouped as high and low,a prominent difference was revealed for overall survival,disease-specific survival,and progression-free *** statistical analysis(univariate Cox),we were also able to identify RFWD3 as an independent prognostic element for HCC,with RFWD3 having an ability to accurately predict HCC prognosis(area under the curve of 0.863).Finally,we have generated prognostic nomograms for probabilities of 1-,3-and 5-year overall survival in HCC via integrating the factors of age,pathologic stage,alpha-fetoprotein level,and RFWD3 expression.

关键词： Hepatocellular carcinoma Ring finger and WD repeat domain 3 immune cell infiltration Bioinformatics

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Comprehensive analysis of clinical and biological value of ING family genes in liver cancer

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2592-2609页

作者： Shi-Cai Liu School of Medical Information Wannan Medical CollegeWuhu 241002Anhui ProvinceChina

BACKGROUND Liver cancer(LIHC)is a malignant tumor that occurs in the liver and has a high mortality in *** ING family genes were identified as tumor suppressor *** expression of these genes can lead to cell cycle arrest,senescence and/or *** family genes are promising targets for anticancer ***,their role in LIHC is still not well *** To have a better understanding of the important roles of ING family members in *** A series of bioinformatics approaches(including gene expression analysis,genetic alteration analysis,survival analysis,immune infiltration analysis,prediction of upstream microRNAs(miRNAs)and long noncoding RNAs(lncRNAs)of ING1,and ING1-related gene functional enrichment analysis)was applied to study the expression profile,clinical relationship,prognostic significance and immune infiltration of ING in *** relationship between ING family genes expression and tumor associated immune checkpoints was investigated in *** molecular mechanism of ING1 mediated hepatocarcinogenesis was preliminarily *** mRNA/protein expression of different ING family genes in LIHC was analyzed in different databases,showing that ING family genes were highly expressed in *** 47 samples from 366 LIHC patients,the ING family genes were altered at a rate of 13%.By comprehensively analyzing the expression,clinical pathological parameters and prognostic value of ING family genes,ING1/5 was ***1/5 was related to poor prognosis of LIHC,suggesting that they may play key roles in LIHC tumorigenesis and *** of the target miRNAs of ING1 was identified as *** upstream lncRNAs of hsa-miR-214-3p,U91328.1,and HCG17,were *** the same time,we found that the expression of ING family genes was correlated with immune cell infiltration and immune checkpoint *** This study lays a foundation for further research on the potential mechanism and clinical v

关键词： Liver cancer ING family genes Noncoding RNAs immune cell infiltration Prognosis

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A prognosis model for predicting immunotherapy response of esophageal cancer based on oxidative stress-related signatures

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Oncology Research 2024年第1期32卷 199-212页

作者： JING GUO CHANGYONG TONG JIANGUANG SHI XINJIAN LI XUEQIN CHEN Department of Thoracic Surgery The First Affiliated Hospital of Ningbo UniversityNingboChina Department of Chinese Traditional Medicine The First Affiliated Hospital of Ningbo UniversityNingboChina

Oxidative stress(OS)is intimately associated with tumorigenesis and has been considered a potential therapeutic ***,the OS-associated therapeutic target for esophageal squamous cell carcinoma(ESCC)remains *** our study,gene expression data of ESCC and clinical information from public databases were *** LASSO-Cox regression analysis,a risk score(RS)signature map of prognosis was constructed and performed external verification with the GSE53625 *** ESTIMATE,xcell,CIBERSORT,TIMER,and ImmucellAI algorithms were employed to analyze infiltrating immune cells and generate an immune microenvironment(IM).Afterward,functional enrichment analysis clarified the underlying mechanism of the *** was utilized for forecasting the survival rate of individual ESCC *** a result,we successfully constructed an OS-related genes(OSRGs)model and found that the survival rate of high-risk groups was lower than that of low-risk *** AUC of the ROC verified the strong prediction performance of the signal in these two cohorts *** to independent prognostic analysis,the RS was identified as an independent risk factor for *** nomogram and follow-up data revealed that the RS possesses favorable predictive value for the prognosis of ESCC ***-PCR detection demonstrated increased expression of MPC1,COX6C,CYB5R3,CASP7,and CYCS in esophageal cancer *** conclusion,we have constructed an OSRGs model for ESCC to predict patients’prognosis,offering a novel insight into the potential application of the OSRGs model in ESCC.

关键词： Esophageal carcinoma OS Prognosis Risk markers immune cell infiltration

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A Prognostic Biomarker for Bladder Cancer Correlated with immune infiltration Is PAEP

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Journal of Biosciences and Medicines 2024年第4期12卷 185-209页

作者： Ning Tang Shasha Gai Qun Huang Nationalities Youjiang Medical University Baise China Nationalities Graduate School Youjiang Medical University Baise China Department of Urology the Affiliated Hospital of Youjiang Medical University for Nationalities Baise China The Affiliated Hospital of Youjiang Medical University for Nationalities Baise China

Background: A major cause of cancer death worldwide is bladder cancer, which is the most common malignant tumor of the urinary tract. PAEP is a member of the kernel lipocalin superfamily whose members share relatively low sequence similarity but have highly conserved exon/intron structure and three-dimensional protein folding. Most lipocalins are clustered on the long arm of chromosome 9. The purpose of this study was to clarify the correlation between PAEP expression level and bladder cancer. Methods: In the TCGA database, we obtained clinical and RNA sequencing data of 431 BLCA patients, including 412 BLCA tissues and 19 normal bladder tissues in the study. Analyses of bioinformatics were conducted in this study to determine the role of PAEP in bladder cancer. A quantitative real-time PCR method was used to quantitate the gene expression profile. Additionally, the effect of PAEP on tumor immune infiltration and prognosis was analyzed. Results: PAEP was a poor prognostic biomarker of bladder cancer because it was significantly upregulated. bladder cancer patients with higher PAEP expression had poor outcomes. An AUC of 0.780 was calculated from the area under the ROC curve. PAEP was associated with T stage, pathologic stage, Histologic grade and Subtype of bladder cancer patients, and served as an independent predictor of overall survival in bladder cancer patients. Functional enrichment analysis revealed PAEP was obviously enriched in pathways connected with carcinogenesis and immunosuppression. The expression of PAEP was significantly associated with tumor immune cells and immune checkpoints according to ssGSEA and Spearman correlation analysis. Conclusions: In this study, we screened and detected a mRNA, PAEP is a prognostic and immune-related biomarker in BLCA, which may contribute to the early diagnosis and treatment of BLCA.

关键词： PAEP Bladder Cancer immune cell infiltration immune Checkpoint Prognosis

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