Abstract

BackgroundRAS association domain family protein 1A (RASSF1A) promoter hypermethylation is suggested to be linked to hepatocellular carcinoma (HCC), but the results remained controversial.MethodsWe evaluated how RASSF1A promoter hypermethylation affects HCC risk and its clinicopathological characteristics through meta-analysis. Data on DNA methylation in HCC and relevant clinical data were also collected based on The Cancer Genome Atlas (TCGA) database to investigate the prognostic role of RASSF1A promoter hypermethylation in HCC.ResultsForty-four articles involving 4777 individuals were enrolled in the pooled analyses. The RASSF1A promoter methylation rate was notably higher in the HCC cases than the non-tumor cases and healthy individuals, and was significantly related to hepatitis B virus (HBV) infection-positivity and large tumor size. Kaplan–Meier survival analysis revealed that HCC cases with RASSF1A promoter hypermethylation had worse outcomes. Receiver operating characteristic curves confirmed that RASSF1A promoter methylation may be a marker of HCC-related prognoses.ConclusionsRASSF1A promoter hypermethylation is a promising biomarker for the diagnosis of HCC from tissue and peripheral blood, and is an emerging therapeutic target against HCC.

Highlights

  • Liver cancer (LC) is the sixth leading cause of cancerrelated morbidity, and the fourth major cause of cancerrelated death, worldwide

  • We found that the frequency of RAS association domain family protein 1A (RASSF1A) gene promoter hypermethylation was remarkably related to a high hepatocellular carcinoma (HCC) risk in the overall comparison, and moderate heterogeneity was present (­ I2 = 64.1%, P = 0.000)

  • We found that RASSF1A promoter hypermethylation is a promising biomarker for the diagnosis of HCC from tissue and peripheral blood

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Summary

Introduction

Liver cancer (LC) is the sixth leading cause of cancerrelated morbidity, and the fourth major cause of cancerrelated death, worldwide. CpG island methylation within gene promoters, key epigenetic regulatory factors, has an important role in HCC initiation and development [5]. Promoter hypermethylation may result in the silencing of some tumor suppressors that regulate the cell signaling pathways in tumor tissues [6,7,8]. The RAS association domain family (2020) 20:547 protein 1A (RASSF1A) is an important tumor suppressor associated with multiple biological functions, and its promoter is frequently blocked due to promoter hypermethylation in numerous malignant tumors, including. RAS association domain family protein 1A (RASSF1A) promoter hypermethylation is suggested to be linked to hepatocellular carcinoma (HCC), but the results remained controversial

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