Identification of 13 Key Genes Correlated With Progression and Prognosis in Hepatocellular Carcinoma by Weighted Gene Co-expression Network Analysis
Identification of 13 Key Genes Correlated With Progression and Prognosis in Hepatocellular Carcinoma by Weighted Gene Co-expression Network Analysis
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通过加权基因共表达网络分析鉴定与肝细胞癌进展和预后相关的13个关键基因
DOI：
10.3389/fgene.2020.00153
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发表时间：
2020-02-28
影响因子：
3.7
通讯作者：
Liu, Quanyan
中科院分区：
文献类型：
--
作者：
Gu, Yang;Li, Jun;Liu, Quanyan
由于缺乏准确的生物标志物和有效的治疗方法，肝细胞癌仍难以早期诊断和治愈。因此，有必要探讨肝细胞癌的发生发展机制，为临床治疗寻找新的生物标志物。我们进行了加权基因共表达网络分析(WGCNA)来寻找与临床信息高度相关的HUB基因。在本研究中，通过对TCGA LIHC数据集的分析，我们发现了13个HUB基因(GTSE1、PLK1、NCAPH、SKA3、LMNB2、SPC25、HJURP、DEPDC1B、CDCA4、UBE2C、LMNB1、PRR11和SNRPD2)与肝癌的组织学分级高度相关。通过对ROC曲线的分析，这13个HUB基因都可以有效地区分肝癌的高级别和低级别。总体生存和无病生存信息显示，这13个Hub基因的高表达导致预后不良。同时，这13个HUB基因在肝癌组织和非肿瘤组织中的表达有显著差异。我们下载了包含相应临床信息的GSE6764，以验证这13个HUB基因的表达。同时，我们进行了实时定量聚合酶链式反应来验证这13个Hub基因在肝癌组织和非肿瘤组织以及高组织学分级和低组织学分级之间的表达趋势的差异。我们还探索了这13个HUB基因的突变和甲基化信息，以供进一步研究。综上所述，WGCNA在本研究中发现了13个与肝癌进展和预后相关的HUB基因，这些HUB基因可能与肝癌的发生发展有关。
Hepatocellular carcinoma (HCC) remains hard to diagnose early and cure due to a lack of accurate biomarkers and effective treatments. Hence, it is necessary to explore the tumorigenesis and tumor progression of HCC to discover new biomarkers for clinical treatment. We performed weighted gene co-expression network analysis (WGCNA) to explore hub genes that have high correlation with clinical information. In this study, we found 13 hub genes (GTSE1, PLK1, NCAPH, SKA3, LMNB2, SPC25, HJURP, DEPDC1B, CDCA4, UBE2C, LMNB1, PRR11, and SNRPD2) that have high correlation with histologic grade in HCC by analyzing TCGA LIHC dataset. All of these 13 hub genes could be used to effectively distinguish high histologic grade from low histologic grade of HCC through analysis of the ROC curve. The overall survival and disease-free survival information showed that high expression of these 13 hub genes led to poor prognosis. Meanwhile, these 13 hub genes had significantly different expression in HCC tumor and non-tumor tissues. We downloaded GSE6764, which contains corresponding clinical information, to validate the expression of these 13 hub genes. At the same time, we performed quantitative real-time PCR to validate the differences in the expression tendencies of these 13 hub genes between HCC tumor tissues and non-tumor tissues and high histologic grade and low histologic grade. We also explored mutation and methylation information of these 13 hub genes for further study. In summary, 13 hub genes correlated with the progression and prognosis of HCC were discovered by WGCNA in our study, and these hub genes may contribute to the tumorigenesis and tumor progression of HCC.