Epigenetic silencing of BLU through interfering apoptosis results in chemoresistance and poor prognosis of ovarian serous carcinoma patients
Journal
Endocrine-Related Cancer
Journal Volume
213
Journal Issue
227
Pages
213-227
Date Issued
2013
Author(s)
Abstract
Epithelial ovarian carcinoma is usually present at the advanced stage, during which the patients generally have poor prognosis. Our study aimed to evaluate the correlation of gene methylation and the clinical outcome of patients with advanced-stage, high-grade ovarian serous carcinoma. The methylation status of eight candidate genes was first evaluated by methylation-specific PCR and capillary electrophoresis to select three potential genes including DAPK, CDH1, and BLU (ZMYND10) from the exercise group of 40 patients. The methylation status of these three genes was further investigated in the validation group consisting of 136 patients. Patients with methylated BLU had significantly shorter progression-free survival (PFS; hazard ratio (HR) 1.48, 95% CI 1.01-2.56, PZ0.013) and overall survival (OS; HR 1.83, 95% CI 1.07-3.11, PZ0.027) in the multivariate analysis. Methylation of BLU was also an independent risk factor for 58 patients undergoing optimal debulking surgery for PFS (HR 2.37, 95% CI 1.03-5.42, PZ0.043) and OS (HR 3.96, 95% CI 1.45-10.81, PZ0.007) in the multivariate analysis. A possible mechanism of BLU in chemoresistance was investigated in ovarian cancer cell lines by in vitro apoptotic assays. In vitro studies have shown that BLU could upregulate the expression of BAX and enhance the effect of paclitaxel-induced apoptosis in ovarian cancer cells. Our study suggested that methylation of BLU could be a potential prognostic biomarker for advanced ovarian serous carcinoma. ? 2013 Society for Endocrinology.
SDGs
Other Subjects
5 aza 2' deoxycytidine; cisplatin; paclitaxel; adult; apoptosis; article; Bax gene; BLU gene; cancer cell culture; cancer grading; cancer prognosis; cancer resistance; cancer risk; cancer staging; capillary electrophoresis; CDH1 gene; CDKN2B gene; cytoreductive surgery; DAPK gene; DLEC1 gene; DNA extraction; epigenetics; female; gene; gene expression; gene silencing; human; human cell; human tissue; major clinical study; methylation; outcome assessment; ovarian serous carcinoma; ovary cancer; ovary carcinoma; overall survival; polymerase chain reaction; progression free survival; rarb gene; RASSF1a gene; recurrent disease; RNA transcription; RUNX3 gene; upregulation; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cisplatin; Drug Resistance, Neoplasm; Epigenomics; Female; Gene Silencing; Humans; Methylation; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Paclitaxel; Prognosis; RNA, Small Interfering; Tumor Markers, Biological; Tumor Suppressor Proteins
Type
journal article