title: Analysis of ERCC1, BRCA1, RRM1 and TUBB3 as predictors of prognosis in patients with non-small cell lung cancer who received cisplatin-based adjuvant chemotherapy: A prospective study.
abstract: Although adjuvant platinum-based chemotherapy has been demonstrated to improve survival in patients with completely resected non-small cell lung cancer (NSCLC), individualized approaches to therapy are urgently required to improve the treatment efficacy and reduce unnecessary toxicity. It was hypothesized in the present study that the protein levels of excision repair cross-complementation group 1 (ERCC1), breast cancer 1 (BRCA1), ribonucleotide reductase M1 (RRM1) and class III β-tubulin (TUBB3) may influence the therapeutic effect of adjuvant cisplatin-based chemotherapy. The expression of ERCC1, BRCA1, RRM1 and TUBB3 in tissues obtained from 84 patients with NSCLC was analyzed in the present non-interventional study by immunohistochemistry prior to adjuvant chemotherapy. All patients received adjuvant cisplatin-based chemotherapy. The primary endpoint in the present study was disease free survival (DFS). Out of the 84 tumors, the expression of ERCC1, BRCA1, RRM1 and TUBB3 was identified in 46 (55%), 11 (13%), 73 (87%) and 76 (90%) tissues, respectively. A beneficial response to adjuvant cisplatin-based chemotherapy in DFS was associated with the absence of the expression of ERCC1 [hazard ratio (HR), 2.166; 95% confidence interval (CI), 1.049-4.474; P=0.037] and BRCA1 (HR, 2.419; 95% CI, 1.127-5.193; P=0.023), but not with the expression status of RRM1 (HR, 0.568; 95% CI, 0.234-1.379; P=0.212) or TUBB3 (HR, 1.874; 95% CI, 0.448-7.842; P=0.39). In addition, patients lacking the expression of ERCC1 and BRCA1 benefited more from adjuvant cisplatin-based chemotherapy compared with patients that expressed either ERCC1 or BRCA1 (HR, 3.102; 95% CI, 1.343-7.163; P=0.008). The expression of ERCC1 and BRCA1 was significantly associated with the DFS time in patients with NSCLC treated with adjuvant cisplatin-based chemotherapy, respectively. The combination of the ERCC1 and BRCA1 expression levels may be a promising prognostic prediction for adjuvant cisplatin-based chemotherapy.
authors: Department of Thoracic Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China; Xiamen Medical Center, Zhongshan Hospital, Fudan University, Xiamen, Fujian 361015, P.R. China.
authors: Zhi-Liang
authors: ZL
authors: Huang
authors: Department of Thoracic Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China; Department of Critical Care Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China.
authors: Xun
authors: X
authors: Cao
authors: Department of Thoracic Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China; Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China.
authors: Ruo-Zhen
authors: RZ
authors: Luo
authors: Graceland Medical Centre, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510623, P.R. China.
authors: You-Fang
authors: YF
authors: Chen
authors: Department of Thoracic Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.
authors: Lin-Chun
authors: LC
authors: Zhu
authors: Department of Thoracic Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.
authors: Zhesheng
authors: Z
authors: Wen
keywords: breast cancer 1; class III β-tubulin; excision repair cross-complementation group 1; non-small cell lung cancer; ribonucleotide reductase M1