title: Methylation of serum insulin-like growth factor-binding protein 7 promoter in hepatitis B virus-associated hepatocellular carcinoma.
abstract: Methylation of gene promoter CpG islands is an important early event in hepatocellular carcinoma (HCC), and detection of cell-free tumor-specific DNA methylation is becoming a useful noninvasive method for HCC. This study was aimed at determining the diagnostic value of serum insulin-like growth factor-binding protein 7 (IGFBP7) promoter methylation in hepatitis B virus-associated HCC. A total of 217 subjects, including 136 HCC patients, 46 patients with chronic hepatitis B (CHB), and 35 healthy controls (HCs), were included. The methylation status of the serum IGFBP7 gene promoter was determined using methylation-specific PCR. The frequency of serum IGFBP7 promoter methylation in HCC patients (89/136, 65%) was significantly higher than that in CHB patients (8/46, 17%; X(2) = 31.883, P < 0.001) and HCs (5/35, 14%; X(2) = 29.429, P < 0.001). Moreover, elevated IGFBP7 methylation frequency was also observed in HCC patients with vascular invasion compared with those without vascular invasion (84 versus 60%, X(2) = 6.633, P = 0.010). The sensitivities of serum IGFBP7 methylation and alpha-fetoprotein (AFP) in detecting HCC were 65 and 57%, respectively. Of note, the combination of IGFBP7 methylation and AFP showed 85% for sensitivity. These results suggest that methylation of the serum IGFBP7 gene promoter may serve as a useful noninvasive biomarker for HCC diagnosis.
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China; Institute of Hepatology, Shandong University, Jinan, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Fan
authors.forename: Shuai
authors.initials: S
authors.lastname: Gao
authors.forename: Feng-Kai
authors.initials: FK
authors.lastname: Sun
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics* / Q000821:virology; D016022:Case-Control Studies; D019175:DNA Methylation; D005260:Female; D006509:Hepatitis B; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018969:Insulin-Like Growth Factor Binding Proteins; D000509:alpha-Fetoproteins; C102529:insulin-like growth factor binding protein-related protein 1