通过挖掘GEO和TCGA数据库评估由九个丙型肝炎病毒诱导基因组成的新型特征在肝癌中的预后价值
Prognostic Value of a Novel Signature With Nine Hepatitis C Virus-Induced Genes in Hepatic Cancer by Mining GEO and TCGA Databases.
作者信息
Wei Jianming, Wang Bo, Gao Xibo, Sun Daqing
机构信息
Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China.
Department of Paediatric Surgery, Tianjin Medical University General Hospital, Tianjin, China.
出版信息
Front Cell Dev Biol. 2021 Jul 16;9:648279. doi: 10.3389/fcell.2021.648279. eCollection 2021.
BACKGROUND
Hepatitis C virus-induced genes (HCVIGs) play a critical role in regulating tumor development in hepatic cancer. The role of HCVIGs in hepatic cancer remains unknown. This study aimed to construct a prognostic signature and assess the value of the risk model for predicting the prognosis of hepatic cancer.
METHODS
Differentially expressed HCVIGs were identified in hepatic cancer data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases using the library ("limma") package of R software. The protein-protein interaction (PPI) network was constructed using the Cytoscape software. Functional enrichment analysis was performed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Univariate and multivariate Cox proportional hazard regression analyses were applied to screen for prognostic HCVIGs. The signature of HCVIGs was constructed. Gene Set Enrichment Analysis (GSEA) compared the low-risk and high-risk groups. Finally, the International Cancer Genome Consortium (ICGC) database was used to validate this prognostic signature. Polymerase chain reaction (PCR) was performed to validate the expression of nine HCVIGs in the hepatic cancer cell lines.
RESULTS
A total of 143 differentially expressed HCVIGs were identified in TCGA hepatic cancer dataset. Functional enrichment analysis showed that DNA replication was associated with the development of hepatic cancer. The risk score signature was constructed based on the expression of , , , , , , , , and . In this study, the risk score was an independent prognostic factor in the multivariate Cox regression analysis [hazard ratio (HR) = 1.433, 95% CI = 1.280-1.605, < 0.001]. The overall survival curve revealed that the high-risk group had a poor prognosis. The Kaplan-Meier Plotter online database showed that the survival time of hepatic cancer patients with overexpression of HCVIGs in this signature was significantly shorter. The prognostic signature-associated GO and KEGG pathways were significantly enriched in the risk group. This prognostic signature was validated using external data from the ICGC databases. The expression of nine prognostic genes was validated in HepG2 and LO-2.
CONCLUSION
This study evaluates a potential prognostic signature and provides a way to explore the mechanism of HCVIGs in hepatic cancer.
背景
丙型肝炎病毒诱导基因（HCVIGs）在调节肝癌肿瘤发展中起关键作用。HCVIGs在肝癌中的作用尚不清楚。本研究旨在构建一个预后特征并评估风险模型对预测肝癌预后的价值。
方法
使用R软件的“limma”包，在来自基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）数据库的肝癌数据中鉴定差异表达的HCVIGs。使用Cytoscape软件构建蛋白质 - 蛋白质相互作用（PPI）网络。使用基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路进行功能富集分析。应用单变量和多变量Cox比例风险回归分析来筛选预后性HCVIGs。构建HCVIGs的特征。基因集富集分析（GSEA）比较低风险和高风险组。最后，使用国际癌症基因组联盟（ICGC）数据库验证此预后特征。进行聚合酶链反应（PCR）以验证9种HCVIGs在肝癌细胞系中的表达。
结果
在TCGA肝癌数据集中共鉴定出143个差异表达的HCVIGs。功能富集分析表明DNA复制与肝癌的发展相关。基于 、 、 、 、 、 、 、 和 的表达构建风险评分特征。在本研究中，风险评分在多变量Cox回归分析中是一个独立的预后因素[风险比（HR）= 1.433，95%置信区间 = 1.280 - 1.605， < 0.001]。总体生存曲线显示高风险组预后不良。Kaplan - Meier Plotter在线数据库显示，该特征中HCVIGs过表达的肝癌患者生存时间明显较短。预后特征相关的GO和KEGG通路在风险组中显著富集。使用ICGC数据库的外部数据验证了此预后特征。在HepG2和LO - 2中验证了9个预后基因的表达。
结论
本研究评估了一种潜在的预后特征，并提供了一种探索HCVIGs在肝癌中作用机制的方法。
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