Serous ovarian carcinoma patients with high alpha-folate receptor had reducing survival and cytotoxic chemo-response

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• 作者：Yu-Li Chen^a ; ^b ; Ming-Cheng Chang^a ; Chia-Yen Huang^a ; ^b ; Ying-Cheng Chiang^a ; ^c ; Han-Wei Lin^a ; Chi-An Chen^a ; Chang-Yao Hsieh^a ; Wen-Fang Cheng^a ; ^d ; ^e ; ^{wenfangcheng@yahoo.com}
• 关键词：Alpha-folate receptor ; Ovarian serous carcinoma ; Chemotherapy ; Apoptosis ; Overall survival
• 刊名：Molecular Oncology
• 出版年：2012
• 出版时间：June, 2012
• 年：2012
• 卷：6
• 期：3
• 页码：360-369
• 全文大小：709 K

文摘

The alpha-folate receptor (¦Á-FR) is highly-expressed in various non-mucinous tumors of epithelial origin, including ovarian carcinoma. The aim of this study was to investigate the relationship between alpha-folate receptor (¦Á-FR) and the clinico-pathologic features and outcomes of serous ovarian carcinoma patients and the possible mechanism of ¦Á-FR to chemo-resistance. Therefore, semi-quantitative reverse-transcription polymerase chain reactions for ¦Á-FR expression were performed in the 91 specimens of serous ovarian carcinomas. The expression of ¦Á-FR in each ovarian cancer tissue specimen was defined as the ratio of density of ¦Á-FR to density of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In?vitro apoptotic experiments were tested in the original OVCAR-3 tumor cells and various OVCAR-3 ¦Á-FR-transfectants. Patients with an increased ¦Á-FR expression level had poorer responses to chemotherapy (per ¦Á-FR expression level increase: odds ratio (OR): 8.97 (95 % confidence interval (CI): 1.40-57.36), p?=?0.021). An increased ¦Á-FR expression level was an independently poor prognostic factor for disease free interval (DFI) (per ¦Á-FR expression level increase: hazard ratio (HR): 2.45 (95 % CI: 1.16-5.18), p?=?0.02) and had a negative impact on overall survival (OS) of these serous ovarian cancer patients (per ¦Á-FR expression level increase: HR: 3.6 (95 % CI: 0.93-13.29), p?=?0.03) by multivariate analyses. ¦Á-FR inhibited cytotoxic drug-induced apoptosis in our in?vitro apoptotic assays. ¦Á-FR could induce chemo-resistance via regulating the expression of apoptosis-related molecules, Bcl-2 and Bax. Therefore, ¦Á-FR can be a potential biomarker for the prediction of chemotherapeutic responses and clinical prognosis. It also could be the target of ovarian cancer treatment.