Epigenetic basis of hepatocellular carcinoma: A network-based integrative meta-analysis
Epigenetic basis of hepatocellular carcinoma: A network-based integrative meta-analysis作者机构：Department of Psychiatry University Health Network and University of Toronto Multi Organ Transplant Program University Health NetworkToronto M5G2N2 Canada Division of Gastroenterology Department of Medicine University Health Network and University of Toronto
出 版 物：《World Journal of Hepatology》 (世界肝病学杂志（英文版）（电子版）)
年 卷 期：2018年第10卷第1期
页 面：155-165页
学科分类：10[医学]
主 题：Network analysis Hepatocellular carcinoma Methylation
摘 要：AIM To identify the key epigenetically modulated genes and pathways in HCC by performing an integrative meta-analysis of all major, well-annotated and publicly available methylation datasets using tools of network *** Pub Med and Gene Expression Omnibus were searched for genome-wide DNA methylation datasets. Patient clinical and demographic characteristics were obtained. DNA methylation data were integrated using the Ingenuity Pathway Analysis, a software package for visualizing and analyzing biological networks. Pathway enrichment analysis was performed using IPA, which also provides literature-driven and computationallypredicted annotations for significant association of genes to curated molecular *** From an initial 928 potential abstracts, we identified and analyzed 11 eligible high-throughput methylation datasets representing 354 patients. A significant proportion of studies did not provide concomitant clinical data. In the promoter region, HIST1H2AJ and SPDYA were the most commonly methylated, whereas HRNBP3 gene was the most commonly hypomethylated. ESR1 and ERK were central genes in the principal networks. The pathways most associated with the frequently methylated genes were G-protein coupled receptor and c AMP-mediated signalling. CONCLUSION Using an integrative network-based analysis approach of genome-wide DNA methylation data of both the promoter and body of genes, we identified G-protein coupled receptor signalling as the most highly associated with HCC. This encompasses a diverse range of cancer pathways, such as the PI3 K/Akt/m TOR and Ras/Raf/MAPK pathways, and is therefore supportive of previous literature on gene expression in HCC. However, there are novel targetable genes such as HIST1H2 AJ that are epigenetically modified, suggesting their potential as biomarkers and for therapeutic targeting of the HCC epigenome.
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