Over-expression of ABCC5 indicates poor prognosis of ovarian cancer and contributes to paclitaxel resistance in ovarian cancer cells

Aim: Chemo-resistance has been the main obstacle for the successful treatment of ovarian cancer. ABCC5 over-expression was reported in several tumors and was claimed to be associated with multi-drug resistance expect ovarian cancer. This study aimed to find if ABCC5 over-expression contributes to the chemo-resistance and poor prognosis of ovarian cancer. Methods and results: Firstly, bioinformatics analysis was used for predicting the significance of ABCC5 mRNA over-expression in ovarian cancer. Bioinformatics analysis showed ABCC5 was significantly over-expressed in ovarian malignant tumors than in the ovarian surface epithelium, moreover it was significantly higher in the ovarian cancer patients with stage Ⅲ-IV than patients with stage I-II(P=0.00001) . The high expression of ABCC5 was correlated with less overall survival (OS) (P=0.012) but not disease free survival (DFS)(P=0. 91) for ovarian cancer patients.Then tissue microarray was applied for further confirmation of ABCC5 protein expression and location in clinical samples which indicated ABCC5 was positive expressed in the chemo-resistant EOC tissues and mainly located in the cytoplasm.The multivariate logistic regression analysis showed FIGO stage (P<0.001) and positive expression of ABCC5 (P<0.0001) were independent risk factors for chemo-resistance in serous EOC. Kaplan-Meier analysis indicated patients with the ABCC5 negative expression showed significantly higher OS (P=0.043) but not DFS (P=0.067) than the ABCC5 positive expression group. Finally, the cell proliferation, cell apoptosis, wounding healing assay and clone formation ability test was applied and pointed to the inhibited expression of ABCC5 in A2780/Taxol cells could facilitate paclitaxel sensitivity. Conclusions: ABCC5 could be used for predicting the chemo-resistance and poor prognosis of ovarian cancer and might be the therapeutic target to the chemo-resistance.