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

J Int Med Res. 2016 Feb;44(1):89-98. doi: 10.1177/0300060515607383. Epub 2016 Jan 5.

Abstract

Objective: To 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.

Methods: KRAS 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.

Results: Patients 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.

Conclusions: KRAS mutation status and BRCA1 tumour expression are potential biomarkers for tailoring chemotherapy and predicting clinical outcome.

Keywords: BCA1; KRAS; Nonsmall cell lung cancer (NSCLC); TYMS; drug response; overall survival; platinum doublets.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • BRCA1 Protein / genetics*
  • BRCA1 Protein / metabolism
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Demography
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Platinum / pharmacology
  • Platinum / therapeutic use*
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Thymidylate Synthase / genetics*
  • Thymidylate Synthase / metabolism
  • Treatment Outcome

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • KRAS protein, human
  • RNA, Messenger
  • Platinum
  • TYMS protein, human
  • Thymidylate Synthase
  • Proto-Oncogene Proteins p21(ras)