Predicting Clinical Chemo-sensitivity Of Primary Ovarian Cancer Using ATP-TCA Combined With Detection Of Drug Resistance Genes

[Background] The standard treatment for ovarian cancer is cytoreductive surgery combined with platinum/paclitaxel chemotherapy,30% to 40% of patients receiving standard treatment still has residual tumor or tumor progression, which is defined as primary platinum/paclitaxel-resistance with poor prognosis. ATP-TCA (adenosine triphosphate-tumor chemo-sensitivity assay) is the most promising in vitro chemo-sensitivity test method with sensitive, rapid and good clinical correlation characteristics. BRCA1, ERCC1, TUBB3 and PRR13 are platinum and paclitaxel resistance associated genes. This study was to explore the combination of two detection methods in predicting platinum/paclitaxel resistance of primary ovarian cancer, improving ovarian cancer individualized treatment effect. There is no similar reports in ovarian cancer in China currently.[Objectives]To evaluate the relationship between ATP-TCA and clinical results; To evaluate BRCA1,ERCC1,TUBB3 and PRR13 mRNA expression levels and relationship with clinical chemo-sensitivity; To improve the clinical chemotherapy sensitivity predictive power for primary ovarian cancer individual treatment by jointing ATP tumor chemo-sensitivity assay and detection of drug resistance genes.[Methods] Forty-seven primary epithelial ovarian tumor samples were collected from the patients who received cytoreductive surgery. Viable ovarian cancer cells obtained from malignant tissue were tested for their in vitro sensitivity to CBP,DDP,PTX and CBP+PTX using ATP-TCA method; At same time, Real-time quantitative PCR was used to analysis BRCA1,ERCC1,TUBB3 and PRR13 mRNA relative expression in forty-six tumor specimens. Both methods' clinical relevance of chemo-sensitivity and the correlation of these two methods test results were statistically analyzed. The effectiveness of the joint prediction on clinical chemo-sensitivity by combining these two methods was evaluated too.[Results]In Vitro DDP,CBP and PTX+CBP results of three programs were significant related with clinical results(P<0.05), in which PTX+CBP in vitro results had extremely significant correlation with clinical results(P<0.001) and predictive consistent rate was 83%. PTX+CBP program predictive sensitivity, predictive specificity, positive predictive value and negative predictive value was 90%,70.6%,84.4% and 80.0% respectively. BRCA1mRNA relative expression logarithm in the clinical-resistant group and the clinical-sensitive group was 0.673±2.143;-1.436±2.594 (P=0.008), ERCC1mRNA relative expression logarithm in the clinical-resistant group and the clinical-sensitive group was-0.529±1.982;-3.188±2.601 (P=0.001), BRCA1 and ERCC1 expression level is negatively correlated with platinum based chemo-sensitivity. PRR13 expression between two groups closed to a significant difference (P=0.074), TUBB3 expression between two groups had no significant difference (P=0.619). When the BRCA1mRNA expression logarithm was on the-0.6, the predictive specificity,positive,predictive value and negative predictive value were 73.3%,75%,84.6% and 60.0% with the best comprehensive assessment. When the ERCC1mRNA expression logarithm was on-1, the predictive sensitivity,specificity,positive predictive value and negative predictive value were 80.0%,68.8%,82.8% and 64.7% with the best comprehensive assessment. BRCA1 and ERCC1 combination can predict the sensitivity of chemotherapeutic sensitivity, specificity, positive predictive value and negative predictive value increased to 86.7%,68.8%,83.9% and 73.3%. ATP-TCA results combined with BRCA1 and ERCC1 when they three indicators all showed resistance was can be of clinical negative predictive value of chemotherapy sensitivity increased to 88.9%.[Conclusions] ATP-TCA is an ideal method of in vitro drug sensitivity testing method, which can effectively predict clinical chemotherapy sensitivity; BRCA1, ERCC1mRNA expression has a negative correlation with the clinical sensitivity of platinum-based chemotherapy; Combination of the drug-resistant associated genes detection method and the ATP-TCA method can increase the predictive effectiveness of ovarian cancer chemosensitivity and guide individual treatment of ovarian cancer.