影响肝细胞癌5年生存期的关键基因分析

Analysis of hub genes affecting five-year survival in liver cancer

目的识别与肝细胞癌(HCC)5年生存期相关的关键基因并探讨其作用机制。方法利用癌症基因组图谱(TCGA)数据库获取HCC基因转录组数据信息及临床表型信息,利用R语言中edgeR包将该转录组数据进行标准化,筛选log FC绝对值>2,FDR<0.01的基因作为表达差异基因,并应用DAVID进行功能和通路富集分析,构建蛋白-蛋白互作网络(PPI),选择PPI连接度(degree)≥8且排名前10位的基因为候选关键基因,最后绘制Kaplan-Meier生存曲线锁定关键基因。结果共得到383个与HCC 5年生存期相关的差异表达基因,通过PPI筛选出10个候选关键基因,进行Kaplan-Meier生存分析,最终确定了8个与HCC 5年生存期密切相关的关键基因,包括GCG、PTH、HTR5A、CRH、CRHR1、CALCA、ADCY2和GAST。结论上述关键基因主要参与神经内分泌调节,与HCC相关的研究鲜有报道,为今后提供新的研究方向。

Objective To identify key genes associated with five-year survival in Hepatocellular carcinoma(HCC)and to explore their mechanisms of action.Methods We used the cancer genome atlas(TCGA)databases for liver cancer gene transcriptome data and clinical phenotype information,along with the R language edgeR package,to carry out the following steps:standardize the transcriptome data,filter the log FC absolute value>2,screen FDR<0.01 genes as expression differences,and perform an enrichment analysis of the functions and application of the DAVID pathway.We then constructed a protein-protein interaction network(PPI)and selected genes in the PPI network with a connection degree of 8 or higher as candidates for the top ten hub genes;a Kaplan-Meier survival curve was drawn to determine the key genes.Results Through the PPI analysis,we identified a total of 383 differentially expressed genes related to fiveyear HCC survival;from these,10 candidate key genes were further investigated via Kaplan-Meier survival analysis.We determined that eight of the candidate key genes are closely associated with HCC five-year survival;these included GCG,PTH,HTR5A,CRH,CRHR1,CALCA,ADCY2,and GAST.Conclusion The identified key genes are mainly involved in neuroendocrine regulation.Given that this association with HCC survival has rarely been reported,the results of the present study provide new directions in cancer research.