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通过加权基因共表达网络分析筛选肝细胞癌特征基因及实验验证

Screening of Feature Genes Related to Hepatocellular Carcinoma by Weighted Gene Co-expression Network Analysis and Experimental Verification

  • 摘要: 为筛选出肝细胞癌(hepatocellular carcinoma, HCC)与临床病理特征相关的特征基因,本研究将公共数据库中肝细胞癌患者的癌和癌旁组织的差异表达基因,通过加权基因共表达网络分析(weighted gene co-expression network analysis, WGCNA)提取与临床特征相关的基因模块,并对其进行GO分析、KEGG富集分析和蛋白质相互作用分析,筛选出关键基因,应用Kaplan-Meier分析其表达与肝癌患者生存情况的关系,并通过RT-qPCR方法在48对肝细胞癌及癌旁组织中对筛选出的特征基因进行验证。结果显示,模块基因主要参与细胞周期、p53信号通路、核分裂等通路和生物学过程;kif11、rrm2等18个基因与肝癌不良预后密切相关(P<0.01)。RT-qPCR结果显示,kif11和rrm2在肝细胞癌组织中高表达,并与肝细胞癌的肿瘤大小、TNM分期、转移相关(P<0.05)。本研究发现kif11和rrm2与肝细胞癌发生发展预后密切相关,为进一步进行基础和临床研究提供初步证据,并为肝细胞癌的治疗提供了新的靶点。

     

    Abstract: In order to screen out the characteristic genes related to clinicopathological features of hepatocellular carcinoma(HCC), this study extracted the gene modules that related to clinical features from the differentially expressed genes between carcinoma and para-carcinoma tissues of HCC patients through weighted gene co-expression network analysis(WGCNA) in the public database. GO, KEGG enrichment and protein-protein interaction analysis were performed on the extracted gene modules to screen out essential genes. Kaplan-Meier was used to analyze the relationship between its expression and the survival of patients with liver cancer. RT-qPCR was employed to verify the selected characteristic genes in 48 pairs of liver carcinoma and para-carcinoma tissues. The results showed that modular genes are mainly involved in cell cycle, p53 signaling pathway, nuclear division and other signaling pathways and biological processes. In addition, 18 genes such as kif11 and rrm2 were closely related to the poor prognosis of HCC(P<0.01). RT-qPCR showed that kif11 and rrm2 were highly expressed in HCC tissues, and were positively correlated with tumor size, TNM stage, and metastasis of HCC(P<0.05). This study found that kif11 and rrm2 were closely related to the development and prognosis of HCC, providing preliminary evidence for further basic and clinical research, and contributing new targets for the treatment of HCC.

     

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