MT1M and MT1G promoter methylation as biomarkers for hepatocellular carcinoma

AIM: To investigate the potential of promoter methylation of two tumor suppressor genes (TSGs) as biomarkers for hepatocellular carcinoma (HCC). METHODS: A total of 189 subjects were included in this retrospective cohort, which contained 121 HCC patients without any history of curative treatment, 37 patients with chronic hepatitis B (CHB), and 31 normal controls (NCs). DNA samples were extracted from 400 mu L of serum of each subject and then modified using bisulfite treatment. Methylation of the promoters of the TSGs (metallothionein 1M, MT1M; and metallothionein 1G, MT1G) was determined using methylation-specific polymerase chain reaction. The diagnostic value of combined MT1M and MT1G promoter methylation was evaluated using the area under the receiver operating characteristic curves. RESULTS: Our results indicated that the methylation status of serum MT1M (48.8%, 59/121) and MT1G (70.2%, 85/121) promoters in the HCC group was significantly higher than that in the CHB group (MT1M 5.4%, 2/37, P < 0.001; MT1G 16.2%, 6/37, P < 0.001) and NC group (MT1M 6.5%, 2/31, P < 0.001; MT1G 12.9%, 4/27, P < 0.001). Aberrant serum MT1M promoter methylation gave higher specificity to discriminate HCC from CHB (94.6%) and NCs (93.5%), whereas combined methylation of serum MT1M and MT1G promoters showed higher diagnostic sensitivity (90.9%), suggesting that they are potential markers for noninvasive detection of HCC. Furthermore, MT1M promoter methylation was positively correlated with tumor size (rs = 0.321, P < 0.001), and HCC patients with both MT1M and MT1G promoter methylation tended to show a higher incidence of vascular invasion or metastasis (P = 0.018). CONCLUSION: MT1M and MT1G promoter methylation may be used as serum biomarkers for noninvasive detection of HCC. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.