title: Aberrant CpG Island Shore Region Methylation of CAV1 Is Associated with Tumor Progression and Poor Prognosis in Gastric Cardia Adenocarcinoma.
abstract: OBJECTIVE
  Caveolin-1 (CAV1) is a multifunctional scaffolding protein and plays an important role in tumorigenesis. However, the epigenetic changes of CAV1 in gastric cardia adenocarcinoma (GCA) have not been investigated so far. The purpose of this study was to clarify the contribution of critical CpG sites in CAV1 to progression/prognosis of GCA and to further elucidate the effect of critical CpG sites on the ectopic expression of β-catenin in GCA.
  
  
  METHODS
  Methylation-specific polymerase chain reaction (MSP) and bisulfite genomic sequencing (BGS) methods were, respectively, applied to examine the methylation status of CAV1. RT-PCR and immunohistochemistry methods were used to determine the mRNA and protein expression of CAV1 and β-catenin.
  
  
  RESULTS
  Decreased mRNA and protein expression of CAV1 were observed in GCA tumor tissues and were associated with hypermethylation of CpG island shore and transcription start site (TSS) regions in CAV1. Hypermethylation of the other two regions within CpG islands in CAV1 was observed both in tumor and corresponding adjacent tissues but was not related to the transcriptional inhibition of CAV1. The methylation status of CpG island shore region in CAV1 was associated with the ectopic expression of β-catenin and was independently associated with survival in GCA patients.
  
  
  CONCLUSIONS
  Hypermethylation of CpG island shore and TSS regions is cancer specific and is closely associated with reduced expression of CAV1. The CpG island shore methylation of CAV1 may play an important role in progression of GCA and may serve as a prognostic methylation biomarker for GCA patients.
authors.affiliation: Laboratory of Pathology, Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Yan-Li
authors.initials: YL
authors.lastname: Guo
authors.affiliation: Department of Immunology, Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Hebei Medical University, Shijiazhuang, Hebei, China; Department of Medical Oncology, Bethune International Peace Hospital, Shijiazhuang, Hebei, China. Electronic address: zhutienian@163.com.
authors.forename: Tie-Nian
authors.initials: TN
authors.lastname: Zhu
authors.affiliation: Laboratory of Pathology, Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.affiliation: Laboratory of Pathology, Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Dong
authors.affiliation: Laboratory of Pathology, Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Medical Oncology, Bethune International Peace Hospital, Shijiazhuang, Hebei, China.
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Cui
authors.affiliation: Department of Immunology, Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Rui-Jing
authors.initials: RJ
authors.lastname: Zhao
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D002299:Cardia / Q000473:pathology*; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D018899:CpG Islands; D019175:DNA Methylation; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C495540:CAV1 protein, human; D051242:Caveolin 1; D012333:RNA, Messenger; D051176:beta Catenin
keywords: Caveolin-1 gene; Gastric cardia adenocarcinoma; Methylation; β-catenin