title: Temporal evolution in caveolin 1 methylation levels during human esophageal carcinogenesis.
abstract: BACKGROUND
  Esophageal cancer ranks eighth among frequent cancers worldwide. Our aim was to investigate whether and at which neoplastic stage promoter hypermethylation of CAV1 is involved in human esophageal carcinogenesis.
  
  
  METHODS
  Using real-time quantitative methylation-specific PCR (qMSP), we examined CAV1 promoter hypermethylation in 260 human esophageal tissue specimens. Real-time RT-PCR and qMSP were also performed on OE33 esophageal cancer cells before and after treatment with the demethylating agent, 5-aza-2'-deoxycytidine (5-Aza-dC).
  
  
  RESULTS
  CAV1 hypermethylation showed highly discriminative ROC curve profiles, clearly distinguishing esophageal adenocarcinomas (EAC) and esophageal squamous cell carcinomas (ESCC) from normal esophagus (NE) (EAC vs. NE, AUROC = 0.839 and p < 0.0001; ESCC vs. NE, AUROC = 0.920 and p < 0.0001). Both CAV1 methylation frequency and normalized methylation value (NMV) were significantly higher in Barrett's metaplasia (BE), low-grade and high-grade dysplasia occurring in BE (D), EAC, and ESCC than in NE (all p < 0.01, respectively). Meanwhile, among 41 cases with matched NE and EAC or ESCC, CAV1 NMVs in EAC and ESCC (mean = 0.273) were significantly higher than in corresponding NE (mean = 0.146; p < 0.01, Student's paired t-test). Treatment of OE33 EAC cells with 5-Aza-dC reduced CAV1 methylation and increased CAV1 mRNA expression.
  
  
  CONCLUSIONS
  CAV1 promoter hypermethylation is a frequent event in human esophageal carcinomas and is associated with early neoplastic progression in Barrett's esophagus.
authors.affiliation: Department of Pathology, The Shenzhen University School of Medicine, 3688 Nanhai Ave, Rm 703, Nanshan, Shenzhen 518060, Guangdong, People's Republic of China. zhejin1995@yahoo.com.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Jin
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Cao
authors.forename: Yulan
authors.initials: Y
authors.lastname: Cheng
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.forename: Xianling
authors.initials: X
authors.lastname: Feng
authors.forename: Si
authors.initials: S
authors.lastname: Chen
authors.forename: Huimin
authors.initials: H
authors.lastname: Yu
authors.forename: Wenjing
authors.initials: W
authors.lastname: Wu
authors.forename: Zhenfu
authors.initials: Z
authors.lastname: Zhao
authors.forename: Ming
authors.initials: M
authors.lastname: Dong
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Xinmin
authors.initials: X
authors.lastname: Fan
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Mori
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Meltzer
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019540:Area Under Curve; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001471:Barrett Esophagus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077209:Decitabine; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D012372:ROC Curve; D013997:Time Factors
chemical_list: C495540:CAV1 protein, human; D051242:Caveolin 1; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine