title: Hypermethylation of ACP1, BMP4, and TSPYL5 in Hepatocellular Carcinoma and Their Potential Clinical Significance.
abstract: OBJECTIVE
  Aberrant methylation of specific genes is frequent event in hepatocellular carcinoma (HCC). Our present study aims to explore the methylation levels of acid phosphatase locus 1 (ACP1), bone morphogenetic protein 4 (BMP4), and testis-specific protein, Y-encoded-like 5 (TSPYL5) and their potential clinical applications in HCC.
  
  
  METHODS
  The methylation levels of ACP1, BMP4 and TSPYL5 were analyzed in 188 HCC tissues, 163 matched adjacent non-tumor tissues, and 29 normal liver tissues using a method of methylation-sensitive restriction enzyme-based quantitative PCR, and their associations with clinicopathological features and prognosis were evaluated.
  
  
  RESULTS
  Compared with adjacent non-tumor tissues and normal liver tissues, the methylation levels of ACP1, BMP4, and TSPYL5 were significantly increased in HCC tissues (All p < 0.0001). The methylation of each individual gene could distinguish HCC tissues well from adjacent non-tumor tissues with the area under the receiver operating characteristic curves (AUC) of 0.753, 0.785 and 0.917, respectively. Furthermore, a higher methylation of BMP4 was statistically associated with worse disease-free survival (p = 0.006) and might be an independent unfavorable factor for disease-free survival by univariate and multivariate analysis (p = 0.011, HR 3.431, 95 % CI 1.333-8.833).
  
  
  CONCLUSIONS
  Our findings suggest that hypermethylation of ACP1, BMP4, and TSPYL5 are common events in HCC and could be used as potentially detectable biomarkers in HCC tissues. Moreover, BMP4 could be potentially served as a methylated biomarker to predict recurrence and metastasis after hepatectomy for HCC patients. However, their potential clinical application value need to be further clarified.
authors.affiliation: Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Donghu Rd 169, Wuchang District, Wuhan, 430071, China. qiuxueping2010@whu.edu.cn.
authors.forename: Xueping
authors.initials: X
authors.lastname: Qiu
authors.affiliation: The Third Affiliated Hospital of Sun Yat-sen University, Guanzhou, Guandong, China. hubo304191059@126.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.affiliation: Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Donghu Rd 169, Wuchang District, Wuhan, 430071, China. 0501hyf@163.com.
authors.forename: Yifang
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Pathology, Hubei Cancer Hospital, Wuhan, Hubei, China. dengyunte@126.com.
authors.forename: Yunte
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Donghu Rd 169, Wuchang District, Wuhan, 430071, China. xbwang2013@whu.edu.cn.
authors.forename: Xuebin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Donghu Rd 169, Wuchang District, Wuhan, 430071, China. zhengfang@whu.edu.cn.
authors.forename: Fang
authors.initials: F
authors.lastname: Zheng
mesh_terms: D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000235:genetics*; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D016022:Case-Control Studies; D019175:DNA Methylation; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012372:ROC Curve; D012307:Risk Factors; D013997:Time Factors
chemical_list: C525809:BMP4 protein, human; D014408:Biomarkers, Tumor; D055415:Bone Morphogenetic Protein 4; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C527859:TSPYL5 protein, human; C490429:ACP1 protein, human; D017027:Protein Tyrosine Phosphatases
keywords: ACP1; BMP4; DNA methylation; Hepatocellular carcinoma; TSPYL5