21 October 2017
Int J Med Sci 2014; 11(2):164-171. doi:10.7150/ijms.6745
Aberrant DNA Methylation of G-protein-coupled Bile Acid Receptor Gpbar1 (TGR5) is a Potential Biomarker for Hepatitis B Virus Associated Hepatocellular Carcinoma
1. Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, China
Background: G-protein-coupled bile acid receptor Gpbar1 (TGR5) is a newly identified liver tumor suppressor in carcinogenesis. This present study was therefore to determine the potential value of serum TGR5 promoter methylation in identifying hepatocellular carcinoma (HCC) from chronic hepatitis B (CHB) patients.
Methods: The circulating cell-free DNA (cfDNA) was extracted from a retrospective dataset including 160 HCC, 88 CHB and 45 healthy controls (HCs). Methylation status of TGR5 promoter was examined by methylation-specific polymerase chain reaction (MSP).
Results: Hypermethylation of the TGR5 promoter occurred significantly more frequent in HCC (77/160, 48.13%) than CHB (12/88, 13.64%; p<0.01) and HCs (2/45, 4.44%; p<0.01). The methylation rate of TGR5 in HCC patients ≥60 years old was significantly higher than those <60 years old (p<0.05). Alpha fetoprotein (AFP) had sensitivity of 58.13%, 30.63% and 24.38% at cut-off points of 20, 200 and 400ng/ml respectively; while TGR5 methylation combined AFP had sensitivity of 81.25%, 68.13% and 65%. AFP had specificity of 47.73%, 92.05% and 98.86% at cut-off points of 20, 200 and 400ng/ml respectively; while TGR5 methylation combined AFP had specificity of 38.64%, 78.41% and 85.23%. AFP had Youden index of 0.06, 0.23 and 0.23 at cut-off points of 20, 200 and 400ng/ml respectively; while TGR5 methylation combined AFP had Youden index of 0.20, 0.47 and 0.50.
Conclusions: Our findings strongly suggested the combination of serum TGR5 promoter methylation and AFP enhanced the diagnostic value of AFP alone in discriminating HCC from CHB patients.
Keywords: TGR5, DNA methylation, Hepatocellular carcinoma, MSP, serum
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How to cite this article:
Han LY, Fan YC, Mu NN, Gao S, Li F, Ji XF, Dou CY, Wang K. Aberrant DNA Methylation of G-protein-coupled Bile Acid Receptor Gpbar1 (TGR5) is a Potential Biomarker for Hepatitis B Virus Associated Hepatocellular Carcinoma. Int J Med Sci 2014; 11(2):164-171. doi:10.7150/ijms.6745. Available from http://www.medsci.org/v11p0164.htm