基于生物信息学分析TK1在HCC中的表达及其临床意义

Analysis on expression of TK1 in HCC and its clinical significance based on bioinformatics

目的基于肿瘤数据库,挖掘分析胸苷激酶1(TK1)基因在肝细胞癌(HCC)表达情况,并结合生物信息学方法 ,探讨TK1参与HCC的潜在机制。方法 GEPIA分析HCC基因芯片数据中TK1及核心基因mRNA表达。利用Kaplan-Meier plotter分析HCC组织中TK1及核心基因mRNA表达与患者预后的关系。利用LinkedOmics和cBioPortal分析并获得HCC中与TK1相关的共表达基因集。利用WebGestalt对基因集作GO和KEGG通路富集分析。利用String数据库构建基因集蛋白互作网络(PPI),利用Cytoscape筛选PPI中的核心基因。结果 TK1 mRNA在HCC组织表达显著高于癌旁组织(P <0.01),TK1高表达可显著降低患者总生存时间(P <0.01)。LinkedOmics和cBioPortal分析各得到TK1共表达基因248个和245个,利用VENNY2.1获得交集基因212个。GO分析显示,生物学过程方面TK1共表达基因主要与细胞周期、DNA修复、DNA代谢等相关,细胞组成方面主要与染色体凝缩等相关,分子功能方面主要与DNA的催化活性、核苷-三磷酸酶活性等相关。KEGG通路分析显示,TK1共表达基因主要参与DNA复制、细胞周期、错配修复、同源重组、P53信号途径、细胞衰老等过程。PPI分析显示,CDK1等10个基因是TK1共表达相关核心基因,经验证核心基因均在HCC中高表达,并且高表达核心基因的患者生存时间显著下降。结论生物信息学分析可获得TK1在HCC中表达情况,为探索TK1参与肝细胞癌的机制提供数据支持。

Objective To explore and analyze the expression of thymidine kinase-1(TK1) gene in hepatocellular carcinoma(HCC) based on the tumor database and explore the potential involved mechanism of TK1 in HCC combined with bioinformatics methods. Methods GEPIA was used to analyze the expression of TK1 gene and core gene m RNA in HCC gene chip data. The association of expression of TK1 gene and core gene mRNA in HCC tissues with prognosis of patients was analyzed using Kaplan-Meier plotter. LinkedOmics and cBioPortal were used to analyze and obtain the co-expressed gene set associated with TK1 in HCC tissues. WebGestalt was used to perform GO and KEGG pathway enrichment analysis for the gene set;the String database was used to establish a protein-protein interaction(PPI) network of gene set;Cytoscape was used to screen out the core genes in PPI.Results The expression levels of TK1 and mRNA in HCC tissues were significantly higher than that in tissues adjacent to carcinoma(P < 0.01), and high expression of TK1 significantly shortened the overall survival time of patients(P < 0.01). With LinkedOmics and cBioPortal analysis, 248 and 245 covexpressed genes of TK1 were obtained, respectively, and 212 intersection genes were obtained using VENNY2.1. According to GO analysis, the co-expressed genes of TK1 were mainly associated with cell cycle, DNA repair, DNA metabolic process and others in terms of biological process, associated with condensation of chromosome and others in terms of cellular component, and associated with catalytic activity acting on DNA, nucleoside-triphosphatase activity and others in terms of molecular function. According to KEGG pathway enrichment analysis, the co-expressed genes of TK1 were mainly involved in DNA replication, cell cycle, mismatch repair, homologous recombination, P53 signaling pathway, cellular senescence, etc. PPI analysis showed that 10 genes such as CDK1 were core genes associated with TK1 co-expression, the verified core genes were highly expressed in HCC, and the survival time was significantly reduced in patients with high expression of core genes. Conclusion The expression of TK1 in HCC can be obtained with bioinformatics analysis, which can provide data support for exploring the involved mechanism of TK1 in HCC.