Epigenetic silencing of BLU through interfering apoptosis results in chemoresistance and poor prognosis of ovarian serous carcinoma patients

Ying Cheng Chiang, Ming Cheng Chang, Pao Jen Chen, Meei Maan Wu, Chang-Yao Hsieh, Wen Fang Cheng, Chi An Chen

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)213-227
Number of pages15
JournalEndocrine-Related Cancer
Volume20
Issue number2
DOIs
Publication statusPublished - Apr 2013
Externally publishedYes

Keywords

  • Apoptosis
  • BLU
  • Gene methylation
  • Ovarian carcinoma
  • Paclitaxel

ASJC Scopus subject areas

  • Endocrinology
  • Oncology
  • Cancer Research
  • Endocrinology, Diabetes and Metabolism

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