FHIT and RASSF1A promoter hypermethylation in plasma and tumor tissues from patients with hepatocellular carcinoma

Abstract

Objective To detect aberrant methylation in the promoter of FHIT and RASSFIA genes in peripheral plasma and tumor tissues from patients with hepatocellular carcinoma （HCC） and to determine its clinical significance. Methods The methylation status of FHIT and RASSFIA genes in peripheral plasma and tumor tissues from 36 patients with HCC were detected by methylation-spe- cific polymerase chain reaction（MSP）. The correlation between methylation status in plasma and clini- copathological features was analyzed. Results The frequency of promoter methylation of FHIT in tis- sues was 75% （27/36） and in plasma 52.8% （19/36）, and the correlation coefficient was r=0. 482 （P= 0. 003）. The frequency of promoter methylation of RASSFIA in tumor tissues was 83.3% （30/36） and in plasma 61.1% （22/36）, and the correlation coefficient was r=0. 561 （P=0. 0004）. Aberrant methylation of FHIT, RASSFIA gene in the plasma and tissues had no correlation with the patients＇ clinicopathological features such as gender, age, HBV/HCV infection, hepatic cirrhosis, tumor size, alpha-fetoprotein （AFP） level, pathological grade, staging, vascular tumour thrombus and recurrence. The sensitivity of AFP ≥400 μg/L was 44. 4%, and AFP ≥20 μg/L 69.4M. The sensitivity of FHIT and RASSF1A gene promoter hypermethylation in 36 HCC patients was 72.2%. In 20 patients whose AFP 〈400 μg/L, the frequency of hypermethylation of the two genes together was 80%. When AFP 〈20 μg/L, the frequency of hypermethylation of the two genes together was54.50%. Conclusions There was a significant concordance between plasma and tumor tissue methyla tion profiles. The methylation status in plasma and tumor tissues had no correlation with the patients clinicopathological features. Combining promoter methylation of FHIT and RASSF1A genes was supe riot to AFP in the diagnosis of HCC. Key words: Hepatocellular carcimona; Methylation; Tumor tissue; Plasma