基于生物信息学分析丙肝和乙肝相关肝细胞癌的基因组学差异  

Genomics differences between hepatitis C and hepatitis B related hepatocellular carcinomas based on bioinformatics analysis

作　　者：杜志兴 魏孔孔 宋天亮[1] 王纪泽 杨金伟[1] 周辉年[2] 张泠漪 DU Zhixing;WEI Kongkong;SONG Tianliang;WANG Jize;YANG Jinwei;ZHOU Huinian;ZHANG Lingyi(Department of Oncological Surgery,Lanzhou University Second Hospital,Lanzhou 730030,P.R.China;Department of Hepatoliliary surgery,Lanzhou University Second Hospital,Lanzhou 730030,P.R.China;Department of Hepatology,Lanzhou University Second Hospital,Lanzhou 730030,P.R.China)

机构地区：[1]兰州大学第二医院肿瘤外科,兰州730030 [2]兰州大学第二医院肝胆外科,兰州730030 [3]兰州大学第二医院肝病科,兰州730030

出　　处：《中国普外基础与临床杂志》2021年第12期1604-1611,共8页Chinese Journal of Bases and Clinics In General Surgery

摘　　要：目的探讨丙肝相关肝细胞癌(HCV-HCC)和乙肝相关肝细胞癌(HBV-HCC)的基因表达差异及其潜在的分子机制。方法从公共基因表达数据库下载并整合HCV-HCC和HBV-HCC基因表达矩阵并使用limma包对HCV-HCC和HBV-HCC样本的基因表达水平进行差异分析并确定差异表达基因(DEG);通过基因集富集分析(GSEA)探讨HCV-HCC和HBV-HCC间抑制或激活的基因集差异;使用MCODE筛选出得分最高的关键分子模块及其内的关键基因;通过clusterProfiler包对关键基因的基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析以了解关键分子模块潜在的生物学过程和分子通路;同时利用Kaplan-Meier Plotter数据库评估关键基因对HCC患者总生存情况的影响。结果本研究中共获得HBV-HCC样本119例、HCV-HCC样本163例,共筛选出199个DEGs。GSEA结果显示,与HBV-HCC相比,HCV-HCC激活的基因集主要体现在炎症、补体、基因响应干扰素上调、基因响应KRAS表达上调、核因子-κB-肿瘤坏死因子途径调控的基因以及凋亡基因集,而细胞周期相关的基因集则明显被抑制。共发现8个DEGs所富集的关键分子模块,其包含18个关键基因(IFI27、DDX60、MX1、IRF9、OAS3、OAS1、RSAD2、GBP4、HERC6、ISG15、IFIT1、CMPK2、EPSTI1、IFI44、IFI44L、HERC5、IFITM1、CXCL10),这18个关键基因的GO分析显示生物学过程主要集中在与病毒感染相关的机体反应中、细胞组分主要以宿主细胞为主、分子功能则主要是富集在生物学结合,而KEGG通路富集分析显示其主要参与了病毒感染相关的分子信号通路。18个关键基因中有9个(CXCL10、HERC6、DDX60、IFITM1、IFI27、GBP4、IFI44L、IFI44、MX1)与HCC患者总生存情况有关的基因且预后良好(HR<1,P<0.05),其他9个关键基因与HCC患者预后无关(P>0.05)。结论 HBV-HCC和HCV-HCC之间存在着本质的区别,HCV-HCC的发生主要与病毒感染和病毒诱导机体产生的免疫反应密切相关,�Objective To investigate differentially expressed genes(DEGs) and potential molecular mechanisms between hepatitis C-related hepatocellular carcinoma(HCV-HCC) and hepatitis B-related HCC(HBV-HCC). Methods The data of HCV-HCC and HBV-HCC gene expressions were downloaded and integrated from the public gene expression database, and the limma package was used to investigate the DEGs between the HCV-HCC and HBV-HCC samples. The gene set enrichment analysis(GSEA) was used to explore the differences in suppressed or activated gene sets between the HCV-HCC and HBV-HCC samples, and the MCODE was used to explore the key molecular modules, and then the potential biological processes and molecular pathways of the key molecular modules were analyzed. The effect of key genes on survival of the HCC patients was analyzed by the Kaplan-Meier-Plotter database. Results In this study, 119 HBVHCC samples and 163 HCV-HCC samples were obtained, and the 199 DEGs were screened out. Compared with HBVHCC, the activated gene sets of HCV-HCC were mainly enriched in the gene sets of inflammation, complement, upregulation of genes in response to interferon, up-regulation of genes in response to KRAS, genes regulated by the nuclear factor-κB-tumor necrosis factor pathway, and apoptosis. However, the cell cycle-related gene sets were obviously suppressed. Eight key molecular modules enriched by DEGs were found, which included 18 key genes(IFI27, DDX60,MX1, IRF9, OAS3, OAS1, RSAD2, GBP4, HERC6, ISG15, IFIT1, CMPK2, EPSTI1, IFI44, IFI44 L, HERC5, IFITM1,CXCL10). GO analysis showed that the biological process was mainly concentrated in the body response related to virus infection, the molecular component was mainly in the host cells, and the molecular function was mainly enriched in the biological combination. KEGG analysis showed that the key genes were mainly involved in the molecular signaling pathway related to virus infection. The survival analysis showed that the 9 key genes(CXCL10, HERC6, DDX60, IFITM1,IFI27, GBP4, IFI44 L, IFI44, MX1) were

关 键 词：丙肝相关肝细胞癌 乙肝相关肝细胞癌 生物信息学分析 差异表达基因 

分 类 号：R735.7[医药卫生—肿瘤] R512.6[医药卫生—临床医学] Q811.4[生物学—生物工程]