Aberrant DNA methylation of G-protein-coupled bile acid receptor Gpbar1 (TGR5) is a potential biomarker for hepatitis B Virus associated hepatocellular carcinoma.
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.
1. Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, China ; 2. Institute of Hepatology, Shandong University, Jinan 250012, China.
Li-Yan
LY
Han
1. Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, China ; 2. Institute of Hepatology, Shandong University, Jinan 250012, China.
Yu-Chen
YC
Fan
3. Department of Ultrasound, the General Hospital Jinan Military Region, Jinan 250031, China.
Nan-Nan
NN
Mu
1. Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, China.
Shuai
S
Gao
1. Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, China.
Feng
F
Li
1. Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, China.
Xiang-Fen
XF
Ji
1. Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, China.
Cheng-Yun
CY
Dou
1. Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, China ; 2. Institute of Hepatology, Shandong University, Jinan 250012, China.
Kai
K
Wang
D014408:Biomarkers, Tumor / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000235:genetics* / Q000821:virology; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics / Q000472:pathogenicity; D019694:Hepatitis B, Chronic / Q000150:complications / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D043562:Receptors, G-Protein-Coupled / Q000097:blood / Q000235:genetics*; D000509:alpha-Fetoproteins / Q000235:genetics*
D014408:Biomarkers, Tumor; C473772:GPBAR1 protein, human; D043562:Receptors, G-Protein-Coupled; D000509:alpha-Fetoproteins
DNA methylation; Hepatocellular carcinoma; MSP; TGR5; serum