Identification of TAF1, SAT1, and ARHGEF9 as DNA methylation biomarkers for hepatocellular carcinoma

Abstract

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. K E Y W O R D S alcohol consumption, hepatitis C virus infection, hepatocellular carcinoma, methylation

Comprehensive genomic profile of Chinese lung cancer patients and mutation characteristics of individuals resistant to icotinib/gefitinib

“…In this study, we first reported the correlation between SDHA mutation and tumor stage, indicating its potential predictive value. Although the correlation between TAF1 , BRIP1 , and CBFB mutations and prognosis has been reported, only have been reported in lung cancer 56 – 58 . Our results suggest that these genes may be related to prognosis in Chinese lung cancer patients.…”

The Effect of m6A Methylation Regulatory Factors on the Malignant Progression and Clinical Prognosis of Hepatocellular Carcinoma

“…Studies have reported that genetic variation and epigenetic modification can affect the progression of tumors (31). However, the current studies on epigenetic mechanisms mainly focus on DNA methylation and histone modification, which have been found to affect the occurrence, progression and prognosis of HCC (32)(33)(34)(35)(36)(37). m6A methylation is a newly discovered method of RNA chemical modification, and its role in HCC will be gradually revealed.…”

Hypermethylation of the PZP gene is associated with hepatocellular carcinoma cell proliferation, invasion and migration

“…A number of research studies have unveiled that aberrant DNA Abbreviations 5-aza-dC, 5-aza-2ʹ-deoxycytidine; CGI, CpG island; DEmRNA, differentially expressed mRNA; FC, fold change; HCC, hepatocellular carcinoma; MSP, methylation-specific PCR; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide; NC, negative control; PZP, pregnancy zone protein; SD, standard deviation; TCGA-LIHC, The Cancer Genome Atlas Liver Hepatocellular Carcinoma. methylation is able to facilitate tumor cell proliferation, invasion and migration of colorectal cancer [8], gastric cancer [9], liver cancer [10,11], HCC [12] and so on.…”

“…Aberrant CGI methylation of the gene promoter region can activate proto‐oncogenes or silence tumor suppressor genes, leading to altered expression of downstream key genes and consequently promoting the aberrant proliferation of cancer cells [6]. A number of research studies have unveiled that aberrant DNA methylation is able to facilitate tumor cell proliferation, invasion and migration of colorectal cancer [8], gastric cancer [9], liver cancer [10,11], HCC [12] and so on.…”