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. (C) 2016 IMSS. Published by Elsevier Inc.
基金：
National Natural Science Foundation
of China (No. 81071846, to TNZ; No. 81472335, to WG);
Natural Science Foundation of Hebei Province of China (No.
H2013505059, to TNZ; No. H2013206315, to YLG); Department
of Science and Technology of Hebei Province of China (No.
12396107D, to RJZ, No. 09966114D, and No. 092461102D to
TNZ); Wu Jieping Medical Foundation (No. 320.6750.12604,
No. 320.6750.14063, and No. 320.6799.15005 to TNZ) and the
focal point Project of Hebei Medical Research (No. 20130543,
to YLG).
第一作者机构：[1]Hebei Med Univ, Hosp 4, Hebei Canc Inst, Pathol Lab, Shijiazhuang, Hebei, Peoples R China
通讯作者：
通讯机构：[2]Hebei Med Univ, Key Lab Immune Mechanism & Intervent Serious Dis, Dept Immunol, Zhongshan St 361, Shijiazhuang, Hebei, Peoples R China[3]Bethune Int Peace Hosp, Dept Med Oncol, Shijiazhuang, Hebei, Peoples R China[*1]Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Department of Immunology, Hebei Medical University, Zhongshan East Road No. 361, Shijiazhuang, China[*2]Department of Immunology, Hebei Medical University, Zhongshan East Road No. 361, Shijiazhuang, China
推荐引用方式(GB/T 7714)：
Guo Yan-li,Zhu Tie-nian,Guo Wei,et al.Aberrant CpG Island Shore Region Methylation of CAV1 Is Associated with Tumor Progression and Poor Prognosis in Gastric Cardia Adenocarcinoma[J].ARCHIVES OF MEDICAL RESEARCH.2016,47(6):460-470.doi:10.1016/j.arcmed.2016.10.005.
APA：
Guo, Yan-li,Zhu, Tie-nian,Guo, Wei,Dong, Zhi-ming,Zhou, Zhen...&Zhao, Rui-jing.(2016).Aberrant CpG Island Shore Region Methylation of CAV1 Is Associated with Tumor Progression and Poor Prognosis in Gastric Cardia Adenocarcinoma.ARCHIVES OF MEDICAL RESEARCH,47,(6)
MLA：
Guo, Yan-li,et al."Aberrant CpG Island Shore Region Methylation of CAV1 Is Associated with Tumor Progression and Poor Prognosis in Gastric Cardia Adenocarcinoma".ARCHIVES OF MEDICAL RESEARCH 47..6(2016):460-470
