摘要

Background and Aims. Caveolin-1 (CAV1) is a multifunctional scaffolding protein and plays an important role in tumorigenesis. However, the epigenetic changes of CAVI 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 beta-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 CAVI and beta-catenin. Results. Decreased mRNA and protein expression of CAVI were observed in GCA tumor tissues and were associated with hypermethylation of CpG island shore and transcription start site (TSS) regions in CAVI. Hypermethylation of the other two regions within CpG islands in CAVI 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 CAVI was associated with the ectopic expression of beta-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 CAVI may play an important role in progression of GCA and may serve as a prognostic methylation biomarker for GCA patients.

  • 出版日期2016-8
  • 单位河北医科大学; 中国人民解放军白求恩国际和平医院