BRCA1和TopBP1表达与非小细胞肺癌含铂方案疗效的相关性研究

Association of BRCA1 / Top BP1 Expression and Efficacy of Platinum-Based Chemotherapy in Non-Small Cell Lung Cancer

目的探讨DNA损伤修复蛋白乳腺癌易感基因-1（BRCA1）和拓扑异构酶Ⅱβ结合蛋白1（TopBP1）表达与非小细胞肺癌（non—small cell lung cancer，NSCLC）含铂方案疗效的相关性。方法回顾性收集2008年1月～2012年12月我院诊断为非小细胞肺癌、采用含铂方案治疗的患者资料及病理组织标本，以免疫组织化学染色法检测BRCA1和TopBP1表达，评价BRCA1和TopBP1表达与NSCLC临床特征的相关性，并以Kaplan—Meier生存曲线和Cox比例风险回归模型评价BRCA1和TopBP1表达与非小细胞肺癌含铂方案治疗效果的相关性。结果共101例非小细胞肺癌患者纳入研究，肿瘤组织中BRCA1和TopBP1表达存在显著相关（P〈0．001，r=0．326）；BRCA1和TopBPI与年龄、性别、吸烟状况、病理类型、临床分期均无明显相关性（P〉0．05）；BRCA1表达阴性患者生存期显著高于阳性患者（中位生存期34vs．21months，HR1．913，95％CI：1．161～3．150，P=0．011）。TopBP1表达阴性患者生存期显著高于阳性患者（中位生存期36vs．23months，HR1．931，95％CI：1．157～3．224，P=0．012）。BRCA1和TopBP1表达与疾病进展时间无显著相关性（P〉0．05）。结论BRCA1和TopBP1表达阴性的NSCLC患者含铂方案疗效较好，是潜在的疗效预测生物标志物。

OBJECTIVE To explore the association of BRCA1 and TopBP1 expressions with clinical outcome of non-small cell lung cancer treated with platinum-based chemotherapy. METHODS Clinical data of non-small cell lung cancer treated with platinumbased chemotherapy admitted to our hospital from january 2008 to december 2012 were collected and reviewed. Expression levels of BRCA1 and TopBP1 were detected by method of immunohistochemistry, the correlation of BRCA1 and TopBP1 expression with clinical features of non-small cell lung cancer was evaluated, with kaplan meier survival curve and Cox proportion hazards regression used, the correlattion of BRCA1 and TopBP1 proteins expression with progression-free survival and overall survival of non-small cell lung cancer was accessed. RESULTS Analysis revealed that BRCA1 expression was significantly associated with that of TopBP1 in the set of Chinese patients with non-small cell lung cancer （ P 〈 0. 001, r = 0. 326 ）. There was no significant correlation of BRCA1 with TopBP1 gene expression on gender, age, smoking status, clinical stages and histological types of patients （P 〉 0. 05 ）. Negatives of BRCA1 were associated with longer overall survival time when compared with positives （median overall survival 34 vs. 21 months, P = 0. 011 ）, and the adjusted HRs （95% CI） for overall survival were 1. 913 （1. 161 -3. 150） , respectively. Moreover, patients with negatives of TopBP1 were correlated with longer overall survival time when compared with positives （ median overall survival 36 vs. 23 months, P = 0. 012） , and the adjusted HRs （95% CI） for overall survival were 1. 931 （1. 157 -3. 224）, respectively. There was no significant correlation of BRCA1 and TopBP1 expression with disease progression （ P 〉 0. 05 ）. CONCLUSION The prognosis of patients with non-small cell lung cancer in BRCA1 and TopBP1 express negatives is better, and it is potebtial biomarkers of the predictor of platinum-based chemotherapy in non-small cell lung cancer.