Significance of promoter methylation of multiple tumor suppressor genes in hepatocellular carcinoma

Abstract

Abstract Background Methylation 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. Results The 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. Conclusion Methylated 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.

Keywords

• HCC
• RASSF1A
• CHFR
• MGMT
• GSTP1
• hMLH1