The prognostic and predictive value of KRAS oncogene substitutions in lung adenocarcinoma

Cancer. 2013 Jun 15;119(12):2268-74. doi: 10.1002/cncr.28039. Epub 2013 Mar 22.


Background: The prognostic and therapeutic implications of the spectrum of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) oncogene substitutions in lung cancer remain poorly understood. The objective of this study was to determine whether KRAS oncogene substitutions differed with regard to prognosis or predictive value in lung adenocarcinoma.

Methods: KRAS oncogene substitutions and mutant allele-specific imbalance (MASI) were determined in patients with lung adenocarcinoma, and the associations with overall survival (OS), recurrence-free survival (RFS), and chemotherapy interactions were assessed.

Results: KRAS mutational analysis was performed on 988 lung adenocarcinomas, and 318 KRAS mutations were identified. In this predominantly early stage cohort (78.6% of patients had stage I-III disease), OS and RFS did not differ according to the type of KRAS substitution (OS, P = .612; RFS, P = .089). There was a trend toward better OS in the subset of patients with KRAS codon 13 mutations (P = .052), but that trend was not significant in multivariate analysis (P = .076). RFS did not differ according to codon type in univariate analysis (P = .322). There was a marked difference in RFS based on the presence of MASI in univariate analysis (P = .004) and multivariate analysis (P = .009). A test for interaction was performed to determine whether the effect of chemotherapy on OS and RFS differed based on KRAS substitution type, codon type, or the presence of MASI. That test indicated that there were no differences in the effects of chemotherapy for any of variables examined.

Conclusions: KRAS codon 13 mutations and MASI were identified as candidate biomarkers for prognosis, and it may be useful to incorporate them into prospective studies evaluating novel therapies in KRAS-mutant lung adenocarcinoma.

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / mortality
  • Adenocarcinoma of Lung
  • Adult
  • Aged
  • Aged, 80 and over
  • Amino Acid Substitution
  • Biomarkers, Tumor / genetics*
  • Codon
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Mutation
  • Predictive Value of Tests
  • Prognosis
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins / genetics*


  • Biomarkers, Tumor
  • Codon
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins