Predicting clinical chemo-sensitivity of primary ovarian cancer using adenosine triphosphate-tumor chemosensitivity assay combined with detection of drug resistance genes / 中华妇产科杂志

ABSTRACT

Objective To predict clinical chemotherapy sensitivity of primary ovarian cancer by jointing adenosine triphosphate(ATP) - tumor chemo-sensitivity assay(TCA) method in vitro and detection of drug resistance genes, provide reference for clinical treatment. 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 sensitivity to carboplatin (CBP), cisplatin (DDP), paclitaxel(PTX) and CBP + PTX using ATP-TCA method in vitro; at same time, real-time quantitative PCR was used to analysis BRCA1 and ERCC1 mRNA relative expression in forty-six specimens (1 frozen tumor samples mRNA were not detected due to serious degradation). The relationship between ATP-TCA test results, clinical indicators, and the effectiveness of the joint prediction on clinical chemosensitivity by combining these two methods were statistically analyzed using chi-square test. Results (1)The results showns that three programs of DDP,CBP and PTX + CBP were significantly related with clinical results(P<0.05) in vitro, in which the compliance rate in PTX + CBP program was the highest 83%(39/47) ,and the predictive sensitivity, predictive specificity, positive predictive value, negative predictive value and predictive accurate rate were 90%,71%,84% and 80% ,respectively.PTX + CBP combined in vitro test results was also related with residual tumor size and neoadjuvant chemotherapy, which was more prone to drug resistance with residual tumor larger than 2 cm (P = 0. 023) and with neoadjuvant chemotherapy (P = 0.011). (2) BRCA1 mRNA expression levels in the clinical-resistant group and the clinical-sensitive group was 0.673 ± 2.143 and - 1.436 ± 2.594 (P=0.008), ERCC1 mRNA expression levels in the clinical-resistant group and the clinical-sensitive group was -0.529 ± 1.982 and - 3.188 ±2.601 (P =0.001). There were also significant correlation among the expression levels of BRCA1 ,ERCC1 mRNA and clinical efficacy (P<0.01). (3)ATP-TCA and detection of drug resistance genes combined to predict the clinical application of PTX + CBP resistance may occur in 8/9 cases. Conclusions ATP-TCA may be an ideal method of in vitro drug sensitivity testing method, which could effectively predict clinical chemotherapy sensitivity. 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 chemotherapy of ovarian cancer.