Prognostic genes of hepatocellular carcinoma based on gene coexpression network analysis
Prognostic genes of hepatocellular carcinoma based on gene coexpression network analysis
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DOI：
10.1002/jcb.28441
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发表时间：
2019-07-01
影响因子：
4
通讯作者：
Lin, Jie
中科院分区：
文献类型：
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作者：
Xu, Baojin;Lv, Wu;Lin, Jie
肝细胞癌（HCC）是肝癌中最常见的亚型，其预后受到与复杂基因相互作用相关的恶性进展的影响。然而，目前尚无可用于临床应用的与HCC进展相关的生物标志物。本研究分析了50例正常组织和374例肿瘤组织的RNA测序表达数据，筛选出9225个差异表达基因。然后进行加权基因共表达网络分析，通过计算17个基因模块与临床特征的相关性，确定我们感兴趣的蓝色模块。在蓝色模块中，采用拓扑重叠计算法筛选出前30个基因，并通过搜索这些基因是否经过体外或体内实验验证，将这30个基因分为绿色组（11个基因）和黄色组（19个基因）。绿色组中的基因从未被任何实验验证过，被认为是枢纽基因。随后通过新的数据集GSE 76427和KM Plotter Online Tool对这些枢纽基因进行验证，结果表明10个基因（FBXO 43，ARHGEF 39，MXD 3，VIPR1，DNASE1L3，PHLDA 1，CSRNP 1，ADR2B，C1RL和CDC 37 L1）可以作为HCC的预后和进展生物标志物。综上所述，10个在HCC中从未被提及的基因被鉴定为与患者的恶性进展和预后相关。这些发现可能有助于改善肝癌患者的治疗决策，危险分层和预后预测。
Hepatocellular carcinoma (HCC) is the most common subtype in liver cancer whose prognosis is affected by malignant progression associated with complex gene interactions. However, there is currently no available biomarkers associated with HCC progression in clinical application. In our study, RNA sequencing expression data of 50 normal samples and 374 tumor samples was analyzed and 9225 differentially expressed genes were screened. Weighted gene coexpression network analysis was then conducted and the blue module we were interested was identified by calculating the correlations between 17 gene modules and clinical features. In the blue module, the calculation of topological overlap was applied to select the top 30 genes and these 30 genes were divided into the green group (11 genes) and the yellow group (19 genes) through searching whether these genes were validated by in vitro or in vivo experiments. The genes in the green group which had never been validated by any experiments were recognized as hub genes. These hub genes were subsequently validated by a new data set GSE76427 and KM Plotter Online Tool, and the results indicated that 10 genes (FBXO43, ARHGEF39, MXD3, VIPR1, DNASE1L3, PHLDA1, CSRNP1, ADR2B, C1RL, and CDC37L1) could act as prognosis and progression biomarkers of HCC. In summary, 10 genes who have never been mentioned in HCC were identified to be associated with malignant progression and prognosis of patients. These findings may contribute to the improvement of the therapeutic decision, risk stratification, and prognosis prediction for HCC patients.