Zhao Dan, Zhang Wei, Li Xiao-guang, Wang Xiao-bing, Li Mo, Li Yan-fen, Tian Hai-mei, Song Pei-pei, Liu Jing, Chang Qing-yun, Wu Ling-ying
Department of Gynecologic Oncology, Cancer Hospital & Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Zhonghua Zhong Liu Za Zhi. 2012 Mar;34(3):196-200. doi: 10.3760/cma.j.issn.0253-3766.2012.03.008.
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.
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.
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.
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.
评估原发性卵巢癌中BRCA1、ERCC1、TUBB3和PRR13 mRNA的表达及其与临床化疗敏感性的关系，并评估联合检测BRCA1和ERCC1基因对原发性卵巢癌治疗的预测价值。
收集46例行肿瘤细胞减灭术患者的原发性上皮性卵巢肿瘤样本。采用实时定量PCR分析这些病例中BRCA1、ERCC1、TUBB3和PRR13 mRNA的相对表达。对临床化疗敏感性与检测结果的相关性进行统计学分析。评估联合检测两个耐药基因对临床化疗敏感性的预测效能。
临床耐药组中BRCA1 mRNA相对表达对数为0.673±2.143，临床敏感组为-1.436±2.594（P=0.008）。临床耐药组中ERCC1 mRNA相对表达对数为-0.529±1.982，临床敏感组为-3.188±2.601（P=0.001）。BRCA1和ERCC1表达水平与铂类化疗敏感性呈负相关。两组中PRR13表达无显著差异（P=0.074），两组间TUBB3表达也无显著差异（P=0.619）。当BRCA1 mRNA表达对数截点值为-0.6时，预测敏感性、特异性、阳性预测值和阴性预测值分别为73.3%、75.0%、84.6%和60.0%，综合评估最佳。当ERCC1 mRNA表达对数截点值为-1时，预测敏感性、特异性、阳性预测值和阴性预测值分别为80.0%、68.8%、82.8%和64.7%，综合评估最佳。联合检测BRCA1和ERCC1可将化疗敏感性、特异性、阳性预测值和阴性预测值分别提高至86.7%、68.8%、83.9%和73.3%。
BRCA1和ERCC1 mRNA表达与铂类化疗的临床敏感性呈负相关。联合检测两个耐药相关基因可提高卵巢癌化疗敏感性的预测效能，有利于卵巢癌的个体化治疗。
