Meta-analysis of DNA methylation biomarkers in hepatocellular carcinoma

Abstract

DNA methylation is an epigenetic mechanism in the pathogenesis of hepatocellular carcinoma (HCC). Here, we conducted a systematic meta-analysis to evaluate the contribution of DNA methylation to the risk of HCC. A total of 2109 publications were initially retrieved from PubMed, Web of Science, Cochrane Library, Embase, CNKI and Wanfang literature database. After a four-step filtration, we harvested 144 case-control articles in the meta-analysis. Our results revealed that 24 genes (carcinoma tissues vs adjacent tissues), 17 genes (carcinoma tissues vs normal tissues) and six genes (carcinoma serums vs normal serums) were significantly hypermethylated in HCC. Subgroup meta-analysis by geographical populations showed that six genes (carcinoma tissues vs adjacent tissues) and four genes (carcinoma tissues vs normal tissues) were significantly hypermethylated in HCC. Our meta-analysis identified the correlations between a number of aberrant methylated genes ( p16 , RASSF1A , GSTP1 , p14 , CDH1 , APC , RUNX3 , SOCS1 , p15 , MGMT , SFRP1 , WIF1 , PRDM2 , DAPK1 , RARβ , hMLH1 , p73 , DLC1 , p53 , SPINT2 , OPCML and WT1 ) and HCC. Aberrant DNA methylation might become useful biomarkers for the prediction and diagnosis of HCC.

Identification of the genomic region under epigenetic regulation during non‐alcoholic fatty liver disease progression

“…Increased methylation of the promoter region of the MGMT gene has been reported in hepatocellular carcinoma. 45 In the present study, two DMRs were identified in the body of the MGMT gene, one of which was hypomethylated and the other was hypermethylated. The expression of MGMT was downregulated in the livers of patients with advanced NAFLD.…”

Circulating tumor DNAs and non-coding RNAs as potential biomarkers for hepatocellular carcinoma diagnosis, prognosis and response to therapy

“…Concordance between aberrant methylations in tumor tissues and plasma is generally good, indicating that plasma could represent a tumor surrogate when tissue is not available. The field has been widely investigated and a meta-analysis of these studies has been published [20] . In the diagnostic setting, from the analysis of 150 plasma samples from patients with HCC, benign liver disease (including cirrhosis and chronic inactive hepatitis) and normal controls, Huang and co-workers found that the combined aberrant methylation of four genes (APC, GSTP1, RASSF1A and SFRP1) has a significant diagnostic value for HCC [21] , confirming the results obtained in tumor tissues [22] .…”

Potential of the use of methylation biomarkers for diagnostics and prognosis of hepatocellular carcinoma in liquid biopsy

“…Как подтверждают результаты многочисленных исследований, профили метилирования ц-ДНК в крови пациентов с ГК хорошо согласуются с данными по метилированию ДНК в образцах опухолевой ткани ОБЗОРНЫЕ СТАТЬИ ТОМ 5 / VOL. 5 [29]. В связи с этим поиск опухоль-специфических биомаркеров метилирования в циркулирующих опухолевых ДНК представляется перспективным направлением в диагностике и лечении ГК.…”

“…По данным обширного метаанализа 144 экспериментальных статей, посвященных сравнению профилей метилирования ДНК в нормальных и опухолевых тканях печени, для тканей ГК характерно гиперметилирование промоторов генов APC, WIF1, SFRP1 и CDH1. Кроме того, гиперметилирование генов WIF1 и CDH1 часто отмечается в ц-ДНК из сыворотки крови пациентов с ГК [29].…”

“…По данным метаанализа C. Zhang и соавт., гиперметилирование сайтов в промоторах генов CDKN2A и CDKN2В является одним из наиболее распространенных нарушений метилирования при ГК [29]. Гиперметилирование сайтов в промоторе гена CDKN2A, приводящее к снижению уровня экспрессии р16, отмечается в 60-80 % образцов ГК [49].…”