Prognostic significance of BRCA1, ERCC1, RRM1, and RRM2 in patients with advanced non-small cell lung cancer receiving chemotherapy.

Abstract

The aim of this study was to examine the prognostic value of breast cancer susceptibility gene 1 (BRCA1), excision repair cross-complementation 1 (ERCC1), ribonucleotide reductase subunit M1 (RRM1), and ribonucleotide reductase subunit M2 (RRM2) in patients with advanced non-small cell lung cancer (NSCLC) who received platinum-based chemotherapy. A total of 214 patients with histologically or cytologically confirmed advanced NSCLC were enrolled in this study. The relative complementary DNA (cDNA) quantification for BRCA1, ERCC1, RRM1, and RRM2 was conducted using a fluorescence-based, real-time detection method, and β-actin was used as a reference gene. A strong correlation was observed between ERCC1 and RRM1 messenger RNA (mRNA) levels (P = 0.0385). There were inverse significant correlations between BRCA1 and ERCC1 (P < 0.0001) or RRM1 (P < 0.0001) mRNA levels. As BRCA1 levels increased, the probability of response increased (odds ratio [OR] = 0.49; P < 0.001) and the risk of progression (hazard ratio [HR] = 1.52; P = 0.034) and death (HR = 1.45; P = 0.024) decreased. As ERCC1, RRM1, and RRM2 levels increased, the probability of response decreased (ERCC1, OR = 0.42, P < 0.001; RRM1, OR = 0.85, P = 0.083; RRM2, OR = 0.42, P = 0.005) and the risk of progression (ERCC1, HR = 1.59, P = 0.002; RRM1, HR = 1.48, P = 0.039; RRM2, HR = 1.49, P = 0.041) and death (ERCC1, HR = 1.62, P = 0.008; RRM1, HR = 1.52, P = 0.023; RRM2, HR = 1.48, P = 0.017) increased. At multivariate analysis, low expression of ERCC1 was shown to be an independent predictive factor for response to chemotherapy (P = 0.018), time to progression (P = 0.025), and overall survival (P = 0.038). Furthermore, concomitant low expression levels of ERCC1, RRM1, and RRM2 and the high expression level of BRCA1 were predictive of a better outcome (P = 0.014). This study suggests that the efficacy of platinum-based chemotherapy can be improved when customized according to the mRNA expression of BRCA1, ERCC1, RRM1, and RRM2.