title: Gene methylation profiles as prognostic markers in ovarian clear cell and endometrioid adenocarcinomas.
abstract: Ovarian cancer is a cancer of high mortality. Aberrant gene methylation of tumor suppressor genes has been shown to be related to the development of malignancy. This study aimed to investigate the methylation of various genes in ovarian clear cell adenocarcinoma (OCCA) and ovarian endometrioid adenocarcinoma (OEA) and evaluate methylation biomarkers in terms of patient chemo-response and outcome. Eight candidate genes from 66 OCCA and 51 OEA patients were evaluated by methylation-specific polymerase chain reaction and capillary electrophoresis. Clinico-pathological parameters and patient outcomes were analyzed. The frequencies of gene methylation in RASSF1A (79% vs. 59%, p=0.025), E-cadherin (30% vs. 10%, p=0.011), and DLEC1 (71% vs. 43%, p=0.003) were higher in the patients with OCCA than in those with OEA. The chemo-resistant group had a significantly higher percentage of E-cadherin methylation (36.7% vs. 16.1%, p=0.036) than the chemo-sensitive group. In multivariate analysis (log-rank test), advanced stage (4.79 [2.10-10.94], p<0.001) was the only risk factor for mortality. Those with methylation of more than two out of three genes (E-cadherin, DLEC1, and SFRP5) had a shorter disease-free survival (1.89 [1.07-3.32], p=0.028) and overall survival (3.29 [1.57-6.87], p=0.002) than those with methylation of one or no gene. In advanced-stage malignancies, those with more than two out of the three gene methylations also had a shorter overall survival (3.86 [1.63-9.09], p=0.002) than those with methylation of only one or no gene. Patients with OCCA have different patterns of gene methylation than those with OEA. Methylation of the E-cadherin, DLEC1 and SFRP5 genes can be a prognostic biomarker for OCCA and OEA.
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University Taipei, Taiwan.
authors.forename: Chi-An
authors.initials: CA
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University Taipei, Taiwan ; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University Taipei, Taiwan.
authors.forename: Ying-Cheng
authors.initials: YC
authors.lastname: Chiang
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University Taipei, Taiwan.
authors.forename: Ming-Cheng
authors.initials: MC
authors.lastname: Chang
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University Taipei, Taiwan.
authors.forename: Yu-Hao
authors.initials: YH
authors.lastname: Hu
authors.affiliation: Department of Public Health, Fu-Jen Catholic University New Taipei, City, Taiwan.
authors.forename: San-Lin
authors.initials: SL
authors.lastname: You
authors.affiliation: Department of Pharmacology, McGill University Montreal, Quebec, Canada.
authors.forename: Yeu-Yao Kevin
authors.initials: YY
authors.lastname: Cheng
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, National Cheng-Kung University Tainan, Taiwan.
authors.forename: Cheng-Yang
authors.initials: CY
authors.lastname: Chou
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University Taipei, Taiwan ; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University Taipei, Taiwan ; Graduate Institute of Oncology, College of Medicine, National Taiwan University Taipei, Taiwan.
authors.forename: Wen-Fang
authors.initials: WF
authors.lastname: Cheng
keywords: DLEC1; E-cadherin; RASSF1A; SFRP5; methylation; ovarian clear cell adenocarcinoma; ovarian endometrioid adenocarcinoma