Department of General Surgery, Shantou Central Hospital and The Affiliated Shantou Hospital of Sun Yat-sen University, Shantou, China.
Department of General Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
J Cell Physiol. 2020 Jan;235(1):611-618. doi: 10.1002/jcp.28999. Epub 2019 Jul 8.
Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths worldwide. More than 90% of primary HCC is HCC. Hepatitis C virus (HCV) infection and alcohol consumption have been widely accepted as two major risk factors for developing HCC. Herein, we aimed to identify DNA methylation genes related to both HCV infection and alcohol consumption. In this study, we identified methylation genes that were associated with the risk of HCV infection and alcohol consumption, respectively, by a large-scale bioinformatic analysis. Through PPI network analysis, we revealed the associations between the two types of genes and found six hub genes-TAF1, SAT1, Phospholipase C-beta 2, FGD1, ARHGAP4, and ARHGEF9-that may be associated with both HCV infection and alcohol consumption. Gene Ontology enrichment analysis was used to analyze the function which these genes in the network enriched. Among them, TAF1, SAT1, and ARHGEF9 were methylated genes that have been found to be related to tumor progression in HCC patients. Through independent data sets, we verified the methylation pattern of these six genes in HCC samples that had both HCV infection and alcohol consumption risks. Furthermore, we found that three of the six methylated genes were also associated with the prognosis of HCC patients. To summarize, we identified six hub genes that were associated with both HCV infection and alcohol consumption in the progress of HCC. The six methylation genes that might play an important role in both HCV infection and alcohol consumption would be potential therapy targets for HCC.
肝细胞癌（HCC）是全球癌症相关死亡的主要原因。超过 90%的原发性 HCC 是 HCC。丙型肝炎病毒（HCV）感染和饮酒已被广泛认为是导致 HCC 的两个主要危险因素。在此，我们旨在确定与 HCV 感染和饮酒均相关的 DNA 甲基化基因。在这项研究中，我们通过大规模的生物信息学分析分别确定了与 HCV 感染和饮酒风险相关的甲基化基因。通过 PPI 网络分析，我们揭示了两种类型基因之间的关联，并发现了六个枢纽基因-TAF1、SAT1、磷脂酶 C-β2、FGD1、ARHGAP4 和 ARHGEF9-可能与 HCV 感染和饮酒均相关。基因本体论富集分析用于分析网络中这些基因的功能。其中，TAF1、SAT1 和 ARHGEF9 是已发现与 HCC 患者肿瘤进展相关的甲基化基因。通过独立的数据集，我们验证了具有 HCV 感染和饮酒风险的 HCC 样本中这六个基因的甲基化模式。此外，我们发现这六个甲基化基因中的三个与 HCC 患者的预后也相关。总之，我们确定了六个与 HCC 进展中 HCV 感染和饮酒均相关的枢纽基因。这六个可能在 HCV 感染和饮酒中均发挥重要作用的甲基化基因可能是 HCC 的潜在治疗靶点。
