肿瘤组织中BRCA1和RAP80的表达与非小细胞肺癌铂类化疗预后的相关性研究

Correlation Between the Expression of BRCA1 and RAP80 in Tumor Tissues and the Prognosis of Non-small-cell Lung Cancer Patients Treated with Platinum-based Chemotherapy

关键词:  BRCA1|RAP80|非小细胞肺癌|化疗|预后价值

Key words:  BRCA1|RAP80|non-small cell lung cancer|chemotherapy|prognostic value

摘要:

目的 探讨DNA损伤修复蛋白BRCA1和RAP80表达与非小细胞肺癌(non-small cell lung cancer，NSCLC)铂类化疗预后的相关性。方法 回顾性研究2010年6月—2012年6月在浙江大学医学院附属第一医院使用含铂方案化疗的NSCLC患者相关信息，以免疫组织化学染色法检测患者病理组织标本BRCA1和RAP80的表达，评价BRCA1和RAP80表达与NSCLC临床特征的相关性，并以Kaplan-Meier生存曲线和COX回归风险比例模型评价与NSCLC铂类化疗预后的相关性。结果 共95例NSCLC患者纳入研究，肿瘤组织中BRCA1和RAP80表达存在显著相关性(r=0.229，P=0.026)。BRCA1和RAP80蛋白表达与年龄(<60岁和≥60岁)、性别、PS评分、临床分期等临床特征无统计学差异；而RAP80蛋白表达水平与组织学分型、吸烟状态具有显著相关性(P<0.05)。BRCA1或RAP80蛋白表达阳性患者的中位总生存期(overall survival，OS)显著低于阴性患者(P<0.05)。此外，BRCA1与RAP80二者表达都阴性的患者，中位OS显著长于两者至少其中之一为阳性的患者(P<0.05)。然而，BRCA1和RAP80表达与疾病进展时间无显著相关性。多因素分析结果表明，组织学分型及RAP80表达是NSCLC铂类化疗的独立预后因子(P=0.008和P=0.017)。结论 BRCA1和RAP80表达阴性的NSCLC患者含铂方案化疗可带来明显的生存获益，RAP80是潜在的疗效预测生物标志物。

Abstract:

Objective To explore the correlation of prognosis between BRCA1 and RAP80 in non-small cell lung cancer(NSCLC) treated with platinum-based chemotherapy. Methods Patient-related information of NSCLC and receiving platinum-based chemotherapy in June 2010 to June 2012 in The First Affiliated Hospital, Zhejiang University School of Medicine was retrospectively studied. Immunohistochemical staining was conducted to determine the protein expression of BRCA1 and RAP80 with pathological tissue specimen of the patient, and the correlation between the expression of BRCA1 and RAP80 and the clinical characteristics of NSCLC was determined, then the correlation with the prognosis of platinum-based chemotherapy in NSCLC was evaluated by Kaplan-Meier survival curve and COX regression risk ratio model. Results a total of 95 NSCLC patients were included in the study. A significant correlation was observed between BRCA1 and RAP80 expression(r=0.229, P=0.026). There was no significant difference between the protein expression of BRCA1 and RAP80 and the clinical characteristics including age(<60 years and ≥60 years), sex, PS score, clinical tage and other. However, a significant correlation was observed between the expression of RAP80 protein and histological classification, smoking status(P<0.05). The median overall survival(OS) in patients with BRCA1 expression or positive RAP80 expression was significantly lower than that of negative expression(P<0.05). Besides, the median OS in patients with negative expression of both BRCA1 and RAP80 was significantly longer than that in patients with positive expression of BRCA1 or RAP80(P<0.05). There was no significant correlation between the expression of BRCA1 and RAP80 and the time of tumor progression. multivariate regression analysis showed that RAP80 and histological types were the independent indicators for overall survival in NSCLC treated with platinum-based chemotherapy(P=0.008 and P=0.017). Conclusion NSCLC patients with negative BRCA1 and RAP80 expression can benefit from platinum-based chemotherapy. It is expected that RAP80 will be a potential predictor for chemotherapy in NSCLC patients.