Abstract
BackgroundMethylation of the promoter at CpG islands is a mechanism of silencing tumor suppressor genes and therefore enhances cancer progression. The study aimed to examine promoter methylation frequencies of five tumor suppressor genes in hepatocellular carcinoma and their implication on the first-year outcome of surgical resection of the tumor. Fifty specimens of hepatocellular carcinoma and the adjacent non-tumorous liver tissue were collected from the surgically resected hepatic tumor. The status of promoter methylation of tumor suppressor genes RASSF1A, CHFR, MGMT, GSTP1, and hMLH1 was investigated using methylation-specific polymerase chain reaction.ResultsThe frequency of promoter methylation of these tumor suppressors genes (TSG) genes in hepatocellular carcinoma was significantly higher than non-tumorous tissue all, P < 0.05, with a methylation rate of 80% in RASSF1A, 70% in CHFR, 46% in GSTP1, 56% in MGMT, and 10% in hMLH1. Methylation of RASSF1A, CHFR, and MGMT promoter genes was significantly associated with decreased first-year postoperative survival and increased recurrence of hepatocellular carcinoma, P < 0.05.ConclusionMethylated RASSF1A, CHRF, and MGMT promoters indicated poor prognosis among patients with hepatocellular carcinoma and may serve as potential prognostic indicators in patients with hepatocellular carcinoma.
Highlights
Methylation of the promoter at CpG islands is a mechanism of silencing tumor suppressor genes and enhances cancer progression
This study aimed to examine the methylation status of the promoter regions of five tumor suppressors genes (TSG) Ras association domain family 1 (RASSF1A), Checkpoint with forkhead and ring finger domains (CHFR), GlutathioneS-transferase-pi gene (GSTP1), [O-methylguanine-DNA methyltransferase] (MGMT), and Human mutL homolog (hMLH1) in hepatocellular carcinoma (HCC) tissues and the adjacent normal tissue (ANT) in postoperative resection specimens and to check the association of the methylation status of these genes with some clinical and pathological features of HCC
In this study, a panel of five genes RASSF1A, CHFR, GSTP1, MGMT, and hMLH1 with known tumor suppressor activities were examined for the methylation status of their promoter regions in both HCC and its normal surrounding tissue obtained from surgical resection of the liver tumor
Summary
Methylation of the promoter at CpG islands is a mechanism of silencing tumor suppressor genes and enhances cancer progression. The study aimed to examine promoter methylation frequencies of five tumor suppressor genes in hepatocellular carcinoma and their implication on the first-year outcome of surgical resection of the tumor. Fifty specimens of hepatocellular carcinoma and the adjacent non-tumorous liver tissue were collected from the surgically resected hepatic tumor. The status of promoter methylation of tumor suppressor genes RASSF1A, C HFR, MGMT, GSTP1, and hMLH1 was investigated using methylation-specific polymerase chain reaction. HCV infection is the predominant predisposing factor for HCC in Egypt and Japan, whereas in China and Eastern Africa, aflatoxin exposure and HBV infection are the main risks. Coinfections of HBV with HCV or hepatitis δ virus are the most common risks found in Mongolia [1]. Epigenetic alteration in the DNA with the resulting abnormal gene expression has been postulated to have a role in the different stages of hepatocellular carcinogenesis [3, 4]
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