[The mRNA expression of BRCA1, ERCC1, TUBB3, PRR13 genes and their relationship with clinical chemosensitivity in primary epithelial ovarian cancer].

OBJECTIVE: To evaluate the expression of BRCA1, ERCC1, TUBB3 and PRR13 mRNA and their relationship with clinical chemosensitivity in primary ovarian cancer, and to assess the predictive value of joint detection of both BRCA1 and ERCC1 genes for the treatment of primary ovarian cancer. METHODS: Primary epithelial ovarian tumor samples were collected from 46 patients who underwent cytoreductive surgery. Real-time quantitative PCR was used to analyze the relative expression of BRCA1, ERCC1, TUBB3 and PRR13 mRNA in those cases. The correlation of clinical chemosensitivity and the test results was statistically analyzed. The efficacy of the joint prediction of clinical chemosensitivity by combining the two drug resistance gene detection was evaluated. RESULTS: The BRCA1 mRNA relative expression logarithm in the clinical-resistant group was 0.673±2.143, and clinical-sensitive group -1.436±2.594 (P=0.008). The ERCC1 mRNA relative expression logarithm in the clinical-resistant group was -0.529±1.982 and clinical-sensitive group -3.188±2.601 (P=0.001). BRCA1 and ERCC1 expression level is negatively correlated with platinum-based chemosensitivity. The PRR13 expressions in the two groups were not significantly different (P=0.074), and the TUBB3 expressions between the two groups were also not significantly different (P=0.619). When the intercept point value BRCA1 mRNA expression logarithm was -0.6, the predictive sensitivity, specificity, positive predictive value and negative predictive value were 73.3%, 75.0%, 84.6% and 60.0%, respectively, with the best comprehensive assessment. When the intercept point value of ERCC1 mRNA expression logarithm was -1, the predictive sensitivity, specificity, positive predictive value and negative predictive value were 80.0%, 68.8%, 82.8% and 64.7%, respectively, with the best comprehensive assessment. The combination detection of BRCA1 and ERCC1 can improve the chemotherapeutic sensitivity, specificity, positive predictive value and negative predictive value to 86.7%, 68.8%, 83.9% and 73.3%, respectively. CONCLUSIONS: BRCA1 and ERCC1 mRNA expression has a negative correlation with the clinical sensitivity of platinum-based chemotherapy. Combination detection of the two drug-resistance associated genes can improve the predictive efficacy of ovarian cancer chemosensitivity and beneficial to individual treatment of ovarian cancer.

[Predicting clinical chemo-sensitivity of primary ovarian cancer using adenosine triphosphate-tumor chemosensitivity assay combined with detection of drug resistance genes].

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 chemo-sensitivity 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.

[Application of ATP-tumor chemosensitivity assay in recurrent epithelial ovarian cancer].

OBJECTIVE: To explore the value of adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA) in individualized treatment of recurrent epithelial ovarian cancer (REOC), and to evaluate the correlation between the in vitro chemosensitivity assay and clinical drug sensitivity. METHODS: Sixty-nine REOC specimens were tested by ATP-TCA assay retrospectively. The patients were divided into strong sensitive, moderate sensitively and resistant groups according to the ATP-TCA assay results. The clinical results were evaluated according to imaging and serum CA125 analysis. The correlation between in vitro ATP-TCA assay and clinical outcome was statistically analyzed by χ(2) test. The progression free survival (PFS) and overall survival (OS) of each group were analyzed using Kaplan-Meier method. RESULTS: The results of ATP-TCA assay had significant correlation with clinical outcome. The clinical chemotherapy outcome became better with increased drug sensitivity in vitro (χ(2) = 9.066, P = 0.004). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy rate for ATP-TCA method to predict the clinical chemotherapy sensitivity of REOC were 87.5%, 45.9%, 58.3%, 80.9% and 65.2%, respectively. The mean PFS of strong sensitive group, moderately sensitive group and resistant group were 187.1 days, 195.0 days and 60.3 days, respectively. The mean OS were 476.7, 335.7 and 237.5 days, respectively, following the start of TCA-directed therapy. The PFS and OS of the two sensitivity groups in vitro were significantly longer than that of the in vitro-resistant group (P < 0.01). CONCLUSION: The results of ATP-TCA assay are well correlated with clinical treatment responses. The assay may be an important and useful method for individualized chemotherapy for recurrent ovarian cancer.