Prognostic implications of aberrantly expressed methylation-driven genes in hepatocellular carcinoma: A study based on The Cancer Genome Atlas
Prognostic implications of aberrantly expressed methylation-driven genes in hepatocellular carcinoma: A study based on The Cancer Genome Atlas
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肝细胞癌中异常表达的甲基化驱动基因的预后意义：基于癌症基因组图谱的研究
DOI：
10.3892/mmr.2019.10771
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发表时间：
2019-12-01
影响因子：
3.4
通讯作者：
Gong, Xiaobing
中科院分区：
文献类型：
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作者：
Li, Jinzhong;Chen, Ning;Gong, Xiaobing
肝细胞癌（HCC）的RNA测序和甲基化数据从癌症基因组图谱（TCGA）下载。使用Limma软件包和MethylMix算法鉴定HCC和正常组织中异常表达的甲基化驱动基因。注释、可视化和集成发现数据库和ConsensusPathDB用于基因本体论（GO）富集和途径分析。单因素和多因素考克斯回归分析用于构建HCC的预后风险模型。应用生存曲线和受试者工作特征（ROC）曲线评价风险模型的临床实用性。从癌症和正常组织中成功鉴定了总共238个甲基化驱动的基因。GO富集分析表明，这些基因在细胞外空间发挥作用，干扰肝细胞中的脂质代谢并调节适应性免疫应答。总共确定了14个相关途径。生成以下预后风险模型：风险评分= CALML 3（甲基化程度）x（-4.860）+CCNI 2 x（2.071）+TNFRSF 12 A x（-3.369）+IFITM 1 x（1.203）+ENPP 7 P13 x（-1.366）+ DDT x（2.139）+RASAL 2-AS 1 x（-1.384）+ANKRD 22 x（-3.215）。将该模型得出的中位风险评分（0.970）设定为将患者分配到高风险组或低风险组的临界值。高危组5年生存率为35.8%（95%CI =27.1-47.4%），低危组为61.7%（95%CI =51.4-74.2%）（P
RNA-Sequencing and methylation data for hepatocellular carcinoma (HCC) were downloaded from The Cancer Genome Atlas (TCGA). The aberrantly expressed methylation-driven genes in HCC and normal tissues were identified using the Limma package and the MethylMix algorithm. The Database for Annotation, Visualization and Integrated Discovery and ConsensusPathDB were used for Gene Ontology (GO) enrichment and pathway analysis. Univariate and multivariate Cox regression analyses were used to construct a prognostic risk model of HCC. Survival curve and receiver operating characteristic (ROC) curves were applied to evaluate the clinical utility of the risk model. A total of 238 methylation-driven genes were successfully identified from cancer and normal tissues. GO enrichment analysis indicated that these genes functioned in the extracellular space, interfering with lipid metabolism in hepatocytes and regulating adaptive immune responses. In total, 14 relevant pathways were identified. The following prognostic risk model was generated: Risk score=CALML3 (degree of methylation) x (-4.860) + CCNI2 x (2.071) + TNFRSF12A x (-3.369) + IFITM1 x (1.203) + ENPP7P13 x (-1.366) + DDT x (2.139) + RASAL2-AS1 x (-1.384) + ANKRD22 x (-3.215). The median risk score (0.970) derived from this model was set as cutoff value for assigning patients to high- or low-risk group. The 5-year survival rate was 35.8% [95% confidence interval (CI)=27.1-47.4%] in the high-risk group and 61.7% (95% CI=51.4-74.2%) in the low-risk group (P