Aberrant CpG Island Shore Region Methylation of CAV1 Is Associated with Tumor Progression and Poor Prognosis in Gastric Cardia Adenocarcinoma

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• 作者：Yan-li Guo^a ; ^&lowast ; ; Tie-nian Zhu^b ; ^c ; ^&lowast ; ; ^{zhutienian@163.com} ; Wei Guo^a ; Zhi-ming Dong^a ; Zhen Zhou^a ; Yu-jie Cui^c ; Rui-jing Zhao^b ; ^{6810c@163.com}
• 关键词：Caveolin-1 gene ; Methylation ; Gastric cardia adenocarcinoma ; β-catenin
• 刊名：Archives of Medical Research
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：47
• 期：6
• 页码：460-470
• 全文大小：2412 K
• 卷排序：47

文摘

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.MethodsMethylation-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.ResultsDecreased 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.ConclusionsHypermethylation 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.