DNA Methylation Profile of Tumor Suppressor Genes in Diagnosis of Primary Hepatocellular Carcinoma

Objective To investigate the value of promoter methylation status of cancer suppressor genes, such as beclin 1, RASSFA-1, p16, DAPK, etc., and the joint detection in the screening and early diagnosis of hepatocellular carcinoma(HCC). Methods Methylation-specific PCR (MSP) method was used to detect the promoter methylation status of 37 HCC samples and the corresponding tumor adjacent specimens. The area under the ROC curve (AUC) of beclin 1, RASSFA-1, p16, DAPK and stepwise LR results were compared by sensitivity, specificity, Youden index and positive/negative likelihood ratio. Results The positive rates of promoter methylation of beclin 1, RASSFA-1, p16 and DAPK genes in HCC were 5.4% (2/37), 94.6% (35/37), 73.0% (27/37) and 35.1% (13/37), Methylation of RASSFA-1, p16 and DAPK genes was more frequent in HCC than that in adjacent tissues(P<0.05). Combined detection of RASSFA-1 promoter methylation and AFP tumor marker could significantly increase the sensitivity (95.0%) and specificity (97.3%) and the area of ROC(0.903)in the diagnosis of HCC, and obtain higher sensitivity, Youden index and positive/negative likelihood ratio than single gene methylation. Conclusion Joint detection of RASSFA-1 promoter methylation and AFP tumor marker may become an effective index for screening and early diagnosis of HCC.