生物钟相关基因在原发性肝细胞癌中的表达及临床意义

Expression and clinical significance of circadian genes on primary hepatocellular carcinoma: an analysis study based on TCGA database

摘要:

目的： 探究生物钟相关基因在原发性肝细胞癌（简称肝癌）中的表达及意义。方法： 从美国癌症和肿瘤基因图谱数据库（The Cancer Genome Atlas，TCGA）中下载肝癌数据424例，包括374例肝癌患者样本及50例正常对照样本。运用DECenter软件对51个生物钟相关基因进行差异表达分析，比较生物钟基因在肝癌患者及正常样本之间的表达情况。运用DAVID在线工具分析差异基因的GO及KEGG功能富集通路，并通过STRING数据库构建差异基因之间蛋白质相互作用网络。了解生物钟基因肝癌发生发展过程中的主要作用。结果： 在374例肝癌患者样本的51个生物钟相关基因中，有21个基因在肝癌样本中表达上调（P<0.05），3个基因表达下调（P<0.05）。生物钟基因高表达样本主要富集于Wnt信号通路、Hedgehog信号通路及Hippo信号通路（P<0.001）。参与调节昼夜节律和细胞代谢的10个生物钟基因在蛋白质相互作用网络中相关性最为紧密（P<0.001）。GO分析差异基因集中作用于调节昼夜节律、细胞代谢过程、基因表达等通路（P<0.001）。结论： 生物钟相关基因通过调节人体昼夜节律和细胞代谢参与原发性肝细胞癌的发生发展。

Abstract:

Objective: To investigate the relationship between primary hepatocellular carcinoma (HCC) and the expression of circadian genes. Methods: The profiles containing 424 samples were downloaded from The Cancer Genome Atlas (TCGA) of the United States, including 374 cases of hepatoma samples and 50 cases of normal samples. Fifty-one circadian genes were analyzed by DECenter, so as to obtain the differentially expressed genes (DEGs). The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments of DEGs were performed by DAVID online analyses. The protein-protein interaction (PPI) networks of the DEGs were constructed through the STRING database. The circadian genes were studied on its main role in the occurrence and development of HCC. Results: A total of 51 DEGs were identified from 374 cases, among which 21 genes were upregulated (P<0.05) and 3 genes were downregulated (P<0.05). DEGs were mainly involved in the Wnt signaling pathway, Hedgehog signaling pathway and Hippo signaling pathway (P<0.001). Ten DEGs involving in circadian rhythm and regulation of metabolic process were closely associated in the PPI network (P<0.001). GO analysis showed that the biological functions of DEGs focused primarily on circadian rhythm, regulation of metabolic process and regulation of gene expression (P<0.001). Conclusion: DEGs participate in the development of primary HCC through the pathway of circadian rhythm and cell metabolism.