Poor response to platinum-based chemotherapy is associated with KRAS mutation and concomitant low expression of BRAC1 and TYMS in NSCLC.

Abstract

ObjectiveTo evaluate treatment response, survival, and the associations between KRAS mutation status and tumour expression levels of BRCA1, TYMS and SRC retrospectively in a cohort of patients with non-small cell lung cancer (NSCLC), treated exclusively with conjunctive platinum-based doublet chemotherapy.MethodsKRAS mutation status was determined via amplification refractory mutation and multiple quantitative polymerase chain reaction (PCR) analysis. Tumour expression levels of BRCA1, TYMS and SRC were determined via real time quantitative PCR.ResultsPatients with KRAS mutations (n = 3) had significantly shorter survival duration than patients with wild type KRAS (n = 42). Tumour expression levels of BRCA1 and TYMS, but not SRC, were significantly lower in patients with, than in those without, KRAS mutations. Tumour expression level of BRCA1 was positively correlated with survival duration.ConclusionsKRAS mutation status and BRCA1 tumour expression are potential biomarkers for tailoring chemotherapy and predicting clinical outcome.