基于TCGA数据库探索POLA2基因在肝癌中的表达及其与预后的相关性

Expression of POLA2 in Hepatocellular Carcinoma and Its Correlation with Prognosis:an Analysis Based on TCGA Database

目的探索DNA聚合酶α亚基B(POLA2)在肝癌中的表达,分析POLA2表达与肝癌患者临床病理特征和预后的关系。方法利用肿瘤基因组图谱(TCGA)数据库和qRT-PCR技术分析POLA2在肝癌组织及肝癌细胞中的表达水平,利用人类蛋白表达图谱(HPA)数据库评估POLA2蛋白在肝癌组织中的表达水平;应用ROC曲线评估POLA2对肝癌诊断的敏感性,采用Logistic回归分析POLA2表达与肝癌临床病理特征的相关性,通过Kaplan-Meier法、单及多因素Cox回归模型分析POLA2的表达与肝癌患者预后的关系。并进一步寻找TCGA数据库中POLA2共表达基因,进行基因本体(GO)生物功能及京都基因与基因组百科全书(KEGG)通路富集分析。同时通过肿瘤免疫评估资源(TIMER)数据库分析POLA2与肝癌免疫浸润的相关性。结果POLA2在肝癌组织和肝癌细胞中呈显著高表达(均P<0.05),ROC曲线下面积为0.954。POLA2表达与肝癌TNM分期、组织学分级和临床分期均密切相关(均P<0.01),单及多变量Cox分析表明高表达的POLA2可作为肝细胞癌(HCC)的独立生物学标志物。GO生物功能及KEGG通路富集分析提示,POLA2基因可能参与保持解旋酶活性和DNA依赖的ATP酶活性,主要富集于细胞周期、DNA复制和范可尼贫血通路。TIMER数据库分析显示POLA2与免疫浸润细胞(Th2细胞、B细胞、CD4+T细胞、巨噬细胞、中性粒细胞)具有显著正相关(均P<0.01)。结论POLA2表达与肝癌患者预后及免疫浸润具有相关性,可作为肝癌诊断及预后评估的重要生物学靶标。

Objective To explore the expression of DNA polymerase alpha subunit B(POLA2)in hepatocellular carcinoma(HCC),and to analyze its relationship to clinicopathological features and prognosis.Methods The levels of POLA2 expression in HCC tissues and cells were analyzed by the Cancer Genome Atlas(TCGA)and qRT-PCR.Furthermore,the expression of POLA2 protein was evaluated by the Human Protein Atlas(HPA).The sensitivity of POLA2 in the diagnosis of HCC was assessed by ROC curve.The correlation between POLA2 expression and clinicopathological features of HCC was analyzed by Logistic regression.The relationship between POLA2 expression and prognosis was analyzed by the Kaplan-Meier method and univariate and multivariate Cox regression analyses.The co-expressed genes of POLA2 in TCGA database were further searched for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.The correlation between POLA2 and immune infiltration of HCC was analyzed by the Tumor Immune Evaluation Resource(TIMER)database.Results POLA2 was highly expressed in HCC tissues and cells(P<0.05),and the area under the ROC curve was 0.954.The expression of POLA2 was closely related to TNM stage,histological grade and clinical stage(P<0.01).Univariate and multivariate Cox analysis showed that the highly expressed POLA2 could be used as an independent biomarker of HCC.GO biological function and KEGG pathway enrichment analysis suggested that POLA2 might be involved in the maintenance of helicase activity and DNA-dependent ATPase activity.It was mainly enriched in cell cycle,DNA replication and Fanconi anemia pathway.TIMER database analysis showed that POLA2 was positively correlated with immune infiltrating cells(Th2 cells,B cells,CD4+T cells,macrophages and neutrophils)(P<0.01).Conclusion The expression of POLA2 is correlated with the prognosis and immune infiltration of HCC.Therefore,it can be used as an important biological target for diagnosis and prognosis of HCC.