title: Usefulness of plasma epigenetic changes of five major genes involved in the pathogenesis of colorectal cancer.
abstract: OBJECTIVE
  The purpose of present study was to investigate the methylation status of the promoter region in five genes (mothers against decapentaplegic homolog 4, fragile histidine triad protein, death-associated protein kinase 1, adenomatous polyposis coli (APC), and E-cadherin), which are known to be involved in the pathogenesis of colorectal cancer (CRC) and its clinicopathological significance.
  
  
  METHODS
  The study subjects were 60 CRC patients, 40 patients with adenomatous colorectal polyp and 60 healthy control individuals. We further enrolled a total of 16 patients (two patients with Crohn's disease, two patients with ulcerative colitis, one patient with serrated adenoma, and 11 patients with colorectal cancer). The methylation states of the five genes were determined in peripheral blood plasma using methylation-specific polymerase chain reaction single-strand conformation polymorphism analysis.
  
  
  RESULTS
  This study showed the most sensitive epigenetic markers, E-cadherin (60 %), followed by APC (57 %), for detecting CRC. E-cadherin and APC had similar specificities and amplified 84 and 86 %, respectively, of CRC patients compared to non-CRC patients. Additionally, APC was the only marker to be significantly increased (OR = 6.67, 95 % CI = 1.19-23.4, P = 0.045) and the most sensitive (57 %) and specific (89 %) marker in stage I CRC. Though we have not examined the paired cancer tissues and plasma, there was relatively high concordant rate (60-80 %) in our limited number of colorectal cancer patients.
  
  
  CONCLUSIONS
  Five genes, promoter methylation, in plasma were statistically significant risk factors in CRC patients. In this study, E-cad and APC genes may be particularly useful epigenetic biomarkers in plasma for the detection of CRC. Additionally, APC may able to identify early potential CRC.
authors.affiliation: Department of Internal Medicine, Seonam University Namgwang Hospital, Gwang-ju, South Korea.
authors.forename: Seung-Chul
authors.initials: SC
authors.lastname: Pack
authors.forename: Hye-Ran
authors.initials: HR
authors.lastname: Kim
authors.forename: Sang-Woo
authors.initials: SW
authors.lastname: Lim
authors.forename: Hwan-Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Jung-Yun
authors.initials: JY
authors.lastname: Ko
authors.forename: Ki-Sang
authors.initials: KS
authors.lastname: Lee
authors.forename: David
authors.initials: D
authors.lastname: Hwang
authors.forename: Seong-Il
authors.initials: SI
authors.lastname: Park
authors.forename: Hoon
authors.initials: H
authors.lastname: Kang
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Park
authors.forename: Gun-Young
authors.initials: GY
authors.lastname: Hong
authors.forename: Se-Min
authors.initials: SM
authors.lastname: Hwang
authors.forename: Myung-Geun
authors.initials: MG
authors.lastname: Shin
authors.forename: Soong
authors.initials: S
authors.lastname: Lee
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000235:genetics; D000230:Adenocarcinoma / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D018256:Adenomatous Polyps / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D015820:Cadherins / Q000235:genetics; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D019175:DNA Methylation; D064550:Death-Associated Protein Kinases; D044127:Epigenesis, Genetic; D005260:Female; D017491:Genes, APC; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D051901:Smad4 Protein / Q000235:genetics; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D015820:Cadherins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D064550:Death-Associated Protein Kinases; D005819:Genetic Markers; D009363:Neoplasm Proteins; D051901:Smad4 Protein; D000099170:Bis(5'-adenosyl)triphosphatase; C579096:DAPK1 protein, human