Association of the KRAS genotype and clinicopathologic findings of resected non‐small‐cell lung cancer: A pooled analysis of 179 patients

Published:September 16, 2022DOI:


      • 1.The KRAS p.G12V genotype and solid predominant adenocarcinoma phenotype may be independent predictive factors of a poor clinical course in resected early-stage non-small-cell lung cancers.
      • 2. The most common KRAS genotype was p.G12C, followed by p.G12D, p.G12V and p.G12A.
      • 3. In G12V tumors, the stress response, Rhogtpase activity, and amino acid metabolism were increased, and M phase and cell cycle checkpoint and TCF activation by WNT cascade were observed.
      • 4. G12V tumor showed an increase in the expression of SLC28A2 and an increase in the expression of HLA-A, which is a characteristic of the tumor environment. tumor environment.



      This study assessed the clinicopathological background of early-stage KRAS-mutated non-small-cell lung cancer and analyzed the biological process of KRAS-mutated tumor using an RNA sequencing procedure.

      Patients and methods

      We used a cohort of consecutive series of 179 surgically resected early-stage non-small-cell lung cancers harboring KRAS mutations and analyzed the clinicopathological features, including the KRAS genotypes, affecting the recurrence-free survival and prognosis. Consequently, we performed RNA sequencing to determine the gene expression profiles of nineteen KRAS-mutated non-small-cell cancers.


      The most common KRAS genotype was p.G12C (57; 31.8%). A high p-stage (hazard ratio [HR], 4.181; P < 0.0001) and solid predominant adenocarcinoma histology (HR, 2.343; P = 0.0076) were significant independent prognostic factors for the recurrence-free survival. A high p-stage (HR, 3.793; P < 0.0001), solid predominant adenocarcinoma histology (HR, 2.373; P = 0.0147), and KRAS p.G12V genotype (HR, 1.975; P = 0.0407) were significant independent prognostic factors for the overall survival. A gene expression analysis of the two factors revealed the p.G12V genotype to be closer to those of stem cells, and the traits of e an enhanced fatty acid and amino acid metabolism. as well as And a solid predominant phenotype were shown to an acquired a trait that can withstand hypoxia and the effect of prostaglandin-endoperoxide synthase.


      : The KRAS p.G12V genotype and solid predominant adenocarcinoma phenotype may be independent predictive factors of a poor clinical course in resected early-stage non-small-cell lung cancers, possibly due to the differentiation tendency observed in stem cells, the trait of an enhanced fatty acid and amino acid metabolism, and the effect of prostaglandin-endoperoxide synthase.


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