加权基因共表达网络分析联合免疫浸润分析筛选肝癌关键基因  

Screening of key genes in hepatocellular carcinoma by Weighted Gene Co-expression Network analysis combined with immune infiltration analysis

作　　者：刘佳良 王纯 叶明亮 罗杰 洪莹晖 常莹 LIU Jialiang;WANG Chun;YE Mingliang;LUO Jie;HONG Yinghui;CHANG Ying(Dept.of Gastroenterology,Zhongnan Hospital of Wuhan University/Hubei Clinical Center of Intestinal and Colorectal Diseases/&Hubei Key Laboratory of Intestinal and Colorectal Diseases,Wuhan 430071,Hubei,China)

机构地区：[1]武汉大学中南医院消化内科/湖北省肠病临床研究中心/肠病湖北省重点实验室,湖北武汉430071

出　　处：《武汉大学学报（医学版）》2023年第4期480-484,共5页Medical Journal of Wuhan University

基　　金：国家自然科学基金资助项目(编号:81670554);武汉市科技计划资助项目(编号:2020020601012208)。

摘　　要：目的:通过生物信息学方法筛选肝细胞癌中免疫细胞浸润相关的关键基因,为肝癌免疫治疗提供新的思路。方法:从GEO数据库中下载GSE15765肝癌组织的基因表达数据,应用ImmuCellAI数据库对下载的肝癌表达数据进行免疫浸润分析,得到各个肝癌组织中的免疫细胞的浸润评分;在R语言中使用WGCNA包对肝癌表达数据构建加权基因共表达网络,筛选与免疫细胞浸润相关的共表达网络基因模块,挑选相关模块中的枢纽基因(hub gene)。利用Metascape数据库对枢纽基因进行功能富集分析。STRING数据库联合Cytoscape软件用于获取连结度最高的前10个基因,并通过Kaplan-Meier Plotter网站绘制关键基因在肝癌患者中的生存曲线图。结果:R中使用WGCNA分析GEO下载的70例肝细胞癌数据,共得到10个基因模块。分析ImmuCellAI得到的免疫浸润评分与各个基因模块的相关性,并绘制热图;其中,褐色模块和肝癌组织巨噬细胞浸润有着较高的相关性(P<0.001,cor=0.79),筛选模块内免疫相关的枢纽基因共得到72个。功能富集分析显示枢纽基因主要涉及白细胞激活、淋巴细胞激活、吞噬作用、免疫调节等生物学功能。枢纽基因的蛋白质互作网络分析筛选连接度高的基因得到LCP2、ITGB2、TYROBP、CD86等基因;从中挑选LCP2分子作为关键分子,生存分析显示LCP2低表达与肝癌患者预后不良相关(P=0.0054)。结论:LCP2被筛选作为肝细胞癌巨噬细胞浸润的有关的关键基因,可作为肝细胞癌免疫治疗的潜在靶点。Objective:To screen the pivotal gene related to immune cell infiltration in hepatocellular carcinoma(HCC)by bioinformatics methods so as to provide a new target for immunotherapy in HCC.Methods:HCC gene expression data GSE15765 was downloaded from GEO database.Infiltration score of immune cells in each liver cancer tissue sample was obtained from ImmuCellAI.WGCNA package was used to perform weighted gene co-expression network analysis.The modules and hub genes most relevant to immune cells infiltration were screened out.Function enrichment analysis of hub genes was carried out through Metascape website.STRING database and Cytoscape software were used to pick out the top 10 genes with the highest degree of connectivity.Survival curve of the pivotal immune-related gene in HCC was drawn through Kaplan-Meier Plotter website.Results:WGCNA was performed to identified 10 gene modules in 70 HCC samples.The correlation coefficient between the immune infiltration score and each gene module was calculated.Result was shown in the form of heatmap.There was a high correlation between the brown module and the infiltration of macrophages in liver cancer(P<0.001,cor=0.79).A total of 72 immune-related hub genes were choosen in the brown module.Functional enrichment analysis showed that these genes mainly involved in leukocyte activation,lymphocyte activation,phagocytosis,immune regulation and other biological functions.LCP2,ITGB2,TYROBP,CD86,and other genes were screened out through protein interaction network analysis.LCP2 was selected as the pivotal immune-related gene.Survival analysis showed that low expression of LCP2 was associated with poor prognosis of HCC patients(P=0.0054).Conclusion:LCP2 was chosen as a pivotal gene related to the infiltration of macrophages in hepatocellular carcinoma,and it is recommened as a potential target for immunotherapy in hepatocellular carcinoma.

关 键 词：肝细胞癌 免疫浸润 加权基因共表达网络分析 生物信息 

分 类 号：R735.7[医药卫生—肿瘤]