title: EFEMP1 as a novel DNA methylation marker for prostate cancer: array-based DNA methylation and expression profiling.
abstract: OBJECTIVE
  Abnormal DNA methylation is associated with many human cancers. The aim of the present study was to identify novel methylation markers in prostate cancer (PCa) by microarray analysis and to test whether these markers could discriminate normal and PCa cells.
  
  
  METHODS
  Microarray-based DNA methylation and gene expression profiling was carried out using a panel of PCa cell lines and a control normal prostate cell line. The methylation status of candidate genes in prostate cell lines was confirmed by real-time reverse transcriptase-PCR, bisulfite sequencing analysis, and treatment with a demethylation agent. DNA methylation and gene expression analysis in 203 human prostate specimens, including 106 PCa and 97 benign prostate hyperplasia (BPH), were carried out. Further validation using microarray gene expression data from the Gene Expression Omnibus (GEO) was carried out.
  
  
  RESULTS
  Epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) was identified as a lead candidate methylation marker for PCa. The gene expression level of EFEMP1 was significantly higher in tissue samples from patients with BPH than in those with PCa (P < 0.001). The sensitivity and specificity of EFEMP1 methylation status in discriminating between PCa and BPH reached 95.3% (101 of 106) and 86.6% (84 of 97), respectively. From the GEO data set, we confirmed that the expression level of EFEMP1 was significantly different between PCa and BPH.
  
  
  CONCLUSIONS
  Genome-wide characterization of DNA methylation profiles enabled the identification of EFEMP1 aberrant methylation patterns in PCa. EFEMP1 might be a useful indicator for the detection of PCa.
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, South Korea. urokyj@cbnu.ac.kr
authors.forename: Yong-June
authors.initials: YJ
authors.lastname: Kim
authors.forename: Hyung-Yoon
authors.initials: HY
authors.lastname: Yoon
authors.forename: Seon-Kyu
authors.initials: SK
authors.lastname: Kim
authors.forename: Young-Won
authors.initials: YW
authors.lastname: Kim
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Kim
authors.forename: Isaac Yi
authors.initials: IY
authors.lastname: Kim
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D000077209:Decitabine; D057890:Epigenomics; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics; D011470:Prostatic Hyperplasia / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics*; D015203:Reproducibility of Results
chemical_list: D014408:Biomarkers, Tumor; C119630:EFEMP1 protein, human; D016326:Extracellular Matrix Proteins; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine