ERCC1, RRM1, and BRCA1 mRNA expression levels and clinical outcome of advanced non-small cell lung cancer.

Abstract

e18045 Background: Customizing chemotherapy on the basis of biomarkers may improve outcome in advanced non-small cell lung cancer (NSCLC) patients. The purpose of this study was to investigate whether the expressions of DNA repair genes ERCC1 (excision repair cross complementing 1), RRM1 (ribonucleotide reductase subunit M1) and BRCA1 (breast cancer 1) affected clinical outcome in NSCLC patients. Methods: Patients with stage IIIb/IV NSCLC were given platinum-based chemotherapy. Messenger RNA expression levels of ERCC1, BRCA1 and RRM1 were determined by real-time polymerase chain reaction (RT-PCR) with TaqMan probes in the tumor. The relationship between these three genes with chemoresponse and overall survival was analyzed in this study. Results: Eighty-five patients (median age 59 years, range 30..C78) were enrolled into the study. Median overall survival (OS) was 13 months (range 10.8..C15.2). Time to progression (TTP) was 6.1 months (range 5.5..C6.7). Patients with low ERCC1 expression benefited more from a platinum-containing regimen (p = 0.094). Patients with low RRM1 expression benefited more from a gemcitabine- containing regimen. Patients with high BRCA1 expression benefited more from an anti-tubulin containing regimen (p = 0.046). Partial response rate was 42.4%. A statistically significant difference in OS was seen in patients with low ERCC1 levels compared to patients with high ERCC1 ones. (16.5 months vs. 10.0 months, p = 0.045). A significant relationship was observed between expression of ERCC1 and BRCA1 and TTP (6.5 vs. 5.1 months, p = 0.001, 5.2 vs. 6.5 p = 0.019, respectively). High expression of BRCA1 was associated with better survival in the anti-tubulin containing regimen subgroup. (8.7 vs 13.0 p = 0.035) Conclusions: ERCC1, RRM1 and BRCA1 are promising predictive and prognostic biomarkers in advanced non-small cell lung cancer. No significant financial relationships to disclose.