Relation of the methylation state of RUNX3 and p16 gene promoters with hepatocellular carcinoma in Egyptian patients

Abstract

Background: Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy of adults. RUNX3 and p16 are tumor suppressor genes that may be inactivated by hypermethylation which is a key epigenetic mechanism that contributes to the initiation and progression of various types of human carcinomas including HCC. The aim of this study was to assess the association of hypermethylation of RUNX3 and p16 gene promoters with the incidence of HCC in Egyptian patients. The study included 120 subjects: 30 HCC patients, 30 patients with hepatitis C virus (HCV) without cirrhosis, 30 cirrhotic patients, and 30 healthy volunteers. Methylation-specific polymerase chain reaction (PCR) was done for detection of hypermethylated p16 and RUNX3. Serum levels of liver enzymes and albumin were detected spectrophotometrically and alpha fetoprotein (AFP) was measured in serum by ELISA. Results: Methylation of RUNX3 and p16 was detected in 25/30 (83.3%) and 26/30 (86.7%) of HCC patients, respectively. The methylation state of both RUNX3 and p16 genes was significantly higher in HCC patients compared to the control subjects (P = 0.016, OR = 4.38) and (P = 0.014, OR = 4.97), respectively. The methylation of both promoters was associated with higher AFP levels in the serum of all patients. Conclusions: Hypermethylation of RUNX3 and p16 is significantly associated with the development of HCC and may be implicated in its pathogenesis.