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. 2024 Sep 7;150(9):413.
doi: 10.1007/s00432-024-05932-x.

Clinical characteristics of KRAS mutation subtypes in non-small cell lung cancer population in Xinjiang, China, and their impact on the prognosis of immunotherapy

Guomin Gu  1 , Chunling Liu  1 , Xiaodan Zhu  1 , Yan Yang  1 , Shuming Song  2 , Yan Zhao  1 , Gang Sun  3   4
Affiliations

Clinical characteristics of KRAS mutation subtypes in non-small cell lung cancer population in Xinjiang, China, and their impact on the prognosis of immunotherapy

Guomin Gu et al. J Cancer Res Clin Oncol. .

Abstract

Purpose: Non-small cell lung cancer (NSCLC) is a highly fatal malignancy. The Kirsten rat sarcoma viral oncogene (KRAS) gene profoundly impacts patient prognosis. This study aims to explore the correlation between KRAS mutation subtypes, clinical data, and the impact of these subtypes on immunotherapy.

Materials and methods: Tumor samples from 269 NSCLC patients at the Affiliated Cancer Hospital of Xinjiang Medical University were analyzed. Patients received first- or second-line therapy without targeted therapy. Molecular and clinical data were used to analysis KRAS mutation subtypes and treatment outcomes.

Results: KRAS mutations predominantly included G12C, G12D, and G12V subtypes. TP53 had the highest mutation frequency among KRAS mutations, followed by MST1, STK11, and KMT2C. Gender differences were noted among KRAS mutation subtypes, with G12C and G12V mutations prevalent in males, while G12D mutations were less common among males. Smokers exhibited varied KRAS mutation subtypes, with G12C and G12V prevalent in smokers and G12D in nonsmokers. KRAS mutations were mainly in lung adenocarcinoma. TTF-1 and PD-L1 expression differed significantly among KRAS mutations. Patients with G12C and G12V mutations showed higher TMB levels and better immunotherapy outcomes compared to those without KRAS mutations. Conversely, patients with G12D mutations had poorer immunotherapy responses.

Conclusions: KRAS mutation subtypes exhibit distinct clinical and molecular characteristics and varying responses to immunotherapy. G12C and G12V mutations correlate with better immunotherapy outcomes, while G12D mutations are associated with poorer responses.

Keywords: KRAS; Immunotherapy; Mutation; NSCLC; Prognosis.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The summary of the KRAS mutation. A. Landscape of somatic mutations identified in the 90 NSCLC patients with KRAS mutation, the top 30 genes with mutation frequency are shown on the graph. B. Pie charts of NSCLC patients with KRAS mutations. Pie charts showing the proportions of different KRAS mutation subtypes
Fig. 2
Fig. 2
Heatmap of exclusivity and co-occurrence analysis. A. Analysis of genes with co-mutations or mutually exclusive mutations with KRAS mutation. B. Analysis of genes with co-mutations or mutually exclusive mutations with KRAS G12C mutation. C. Analysis of genes with co-mutations or mutually exclusive mutations with KRAS G12D mutations. C. Analysis of genes with co-mutations or mutually exclusive mutations with KRAS G12V mutations
Fig. 3
Fig. 3
Correlation analysis between KRAS mutations and clinical information. Analysis of correlation between KRAS mutation and age (≥ 65 years and < 65 years) (A), gender (B), smoking (C), Pathological features (D) and TTF-1 (E)
Fig. 4
Fig. 4
PD-L1 expression and TMB analysis in different KRAS mutation subtypes. A. Number of patients with different PD-L1 expressions between KRAS mutation and non-KRAS mutation. B. Analysis of TMB in patients with KRAS mutated subtypes and non-KRAS mutated patients
Fig. 5
Fig. 5
The Kaplan-Meier analysis for the prognostic value of KRAS mutations subtypes. A. Kaplan-Meier analyses of the PFS between the KRAS G12C mutation and WT patients who received immunotherapy. B. Kaplan-Meier analyses of the OS between the KRAS G12C mutation and WT patients who received immunotherapy. C. Kaplan-Meier analyses of the PFS between the KRAS G12CV mutation and WT patients who received immunotherapy. D. Kaplan-Meier analyses of the OS between the KRAS G12V mutation and WT patients who received immunotherapy. E. Kaplan-Meier analyses of the PFS between the KRAS G12CD mutation and WT patients who received immunotherapy. F. Kaplan-Meier analyses of the OS between the KRAS G12D mutation and WT patients who received immunotherapy. G. Kaplan-Meier analyses of the PFS between the KRAS other mutations and WT patients who received immunotherapy. H. Kaplan-Meier analyses of the OS between the KRAS other mutations and WT patients who received immunotherapy
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