Gene methylation profiles as prognostic markers in ovarian clear cell and endometrioid adenocarcinomas
Journal
American Journal of Translational Research
Journal Volume
139
Journal Issue
152
Pages
139-152
Date Issued
2015
Author(s)
Abstract
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. ? 2015, E-Century Publishing Corporation. All rights reserved.
SDGs
Other Subjects
deleted in lung and esophageal cancer 1; paired box transcription factor; Ras association domain family protein 1A; secreted frizzled related protein 1; secreted frizzled related protein 5; transcription factor LMX1A; transcription factor RUNX3; unclassified drug; uvomorulin; adult; Article; cancer prognosis; cancer staging; capillary electrophoresis; DNA methylation; endometrium carcinoma; female; human; human tissue; immunoblotting; major clinical study; middle aged; ovary adenocarcinoma; overall survival; physical sensitivity; polymerase chain reaction; reverse transcription polymerase chain reaction
Type
journal article