肝细胞癌相关差异基因的生物信息学及预后分析

Bioinformatics and Prognostic Analysis of Differentially Expressed Genes in Hepatocellular Carcinoma

肝细胞癌是全球癌症相关死亡的主要原因,目前对肝细胞癌的发病机制研究尚不完善,探索肝细胞癌发生、发展相关的分子标志物及其预后具有重要意义。从GEO数据库获得肝细胞癌组织和非癌组织的基因表达阵列数据GSE84402,利用GEO2R筛选差异表达基因;采用DAVID数据库对差异基因进行GO富集分析和KEGG通路分析;通过STRING数据库和Cytoscape软件构建差异表达基因对应的蛋白质相互作用网络,并从网络中筛选出核心基因(hub genes);结合KM plotter数据库的临床信息对hub genes进行预后分析。结果显示:共得到1 307个差异表达基因,其中上调基因741个,下调基因566个,这些差异表达基因主要涉及细胞分裂、细胞周期、DNA复制及物质代谢等生物学过程及生物通路。通过GO、KEGG及蛋白质相互作用网络筛选出BUB1、BUB1B、CCNA2、CCNB1、CCNB2、CDC20、CDK1、MAD2L1、PLK1等9个hub genes,进一步分析发现hub genes均与细胞周期的调控相关,表明细胞周期的调控失常在肝细胞癌的发生、发展过程中具有重要作用。生存分析显示9个hub genes在肝细胞癌患者中均为表达上调的基因,且与患者预后不良相关,这为寻找肝细胞癌患者预后相关生物标志物的研究提供了线索。

Hepatocellular carcinoma(HCC) is the leading cause of cancer-related death worldwide, but the research on the pathogenesis of HCC is still imperfect. It is important to explore its molecular markers and prognosis. Bioinformatics was used to screen HCC related genes. Gene expression profile data GSE84402,which includes data coming from HCC and non-cancer tissues, were obtained from Gene Expression Om-nibus(GEO) database. GEO2 R was used to screen differentially expressed genes(DEGs). GO function and KEGG pathway analyses of DEGs were performed using DAVID database, and the protein-protein interac-tion(PPI) network was constructed using STRING and Cytoscape software, and the hub genes were screened.The prognostic significance of hub genes was analyzed by KM plotter database. A total of 1 307 DEGs were screened, including 741 up-regulated and 566 down-regulated genes. Biological processes and pathway en-richment analyses showed that the DEGs were mainly enriched in cell division, cell cycle, DNA replication and material metabolism. From GO, KEGG and PPI network, BUB1, BUB1 B, CCNA2, CCNB1, CCNB2,CDC20, CDK1, MAD2 L1 and PLK1 were screened as hub genes. Further analysis showed that the 9 hub genes were all related to the regulation of cell cycle, indicating that the abnormal regulation of cell cycle plays an important role in the development of HCC. Survival analysis showed that the 9 hub genes were found to be up-regulated in HCC patients and correlated with poor prognosis. The study would help us find out the biomarkers related to the prognosis of HCC patients.