KRAS gene oncogene substitutions may be predictive in lung adenocarcinoma
medwire News: Researchers have found that certain KRAS oncogene substitutions may have predictive value in lung adenocarcinoma.
Based on a retrospective analysis of 988 banked tumor specimens, trends toward better survival were found in patients with KRAS codon 13 mutations, and worse survival was noted in those with KRAS mutant allele-specific imbalance (MASI). KRAS amino acid (AA) substitution did not affect prognosis.
Liza Villaruz (University of Pittsburgh Cancer Institute, Pennsylvania, USA) and colleagues write in Cancer that "this study is meant to be hypothesis-generating, and the incorporation of these candidate biomarkers in a prospective fashion into clinical trial design will be necessary to define the true predictive value of KRAS mutation subtypes."
The research team sequenced the tumor specimens and performed additional analyses for KRAS codons 12 and 13 and the presence of MASI. Hazard models were used to determine the effects of KRAS mutations and MASI on overall (OS) and recurrence-free survival (RFS) while controlling for demographic factors such as age, gender, disease stage, and smoking history.
Of the 988 tumors, 32.2% had KRAS mutations. Better OS was noted in patients with KRAS codon 13 mutations, though this trend was not statistically significant in multivariate analysis (adjusting for age and disease stage), nor were there differences in RFS between codon types.
A greater risk for tumor recurrence was found in patients who had tumors with MASI in both univariate and multivariate analyses. OS and RFS were the same for each type of KRAS AA substitution.
As well, no differences in chemotherapy effects were seen for any of the assessed variables.
Villaruz and team acknowledge that these results were not found in the context of a randomized clinical trial. Also, they did not look at KRAS wild-type tumors because "the KRAS wild-type population itself is a molecularly heterogeneous population; that is, it includes a significant proportion of patients who are KRAS wild-type but whose tumors harbor other oncogenic drivers… therefore, we chose to focus the current analyses on a purely KRAS-mutant cohort."
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By Stephanie Leveene, medwireNews Reporter