Molecular Characteristics and the Effect of KRAS Mutation on the Prognosis of Immunotherapy in Non-Small Cell Lung Cancer in Xinjiang, China

Purpose: Non-small cell lung cancer (NSCLC) is a malignant tumor with high mortality. The Kirsten rat sarcoma vial oncogene (KRAS) gene can affect patient prognosis. In this study, we aim to explore the impact of KRAS mutation status on the clinical prognosis of NSCLC immunotherapy. Patients and Methods: Collected tumor samples from the Affiliated Cancer Hospital of Xinjiang Medical University and 220 patients with stage III-IV NSCLC were included the study. All patients are on first- or second-line therapy and not on targeted therapy. Based on the molecular profiles and clinical features, we analysis of the effect of KRAS mutation on the treatment outcome of NSCLC. Results: In this study, the main mutant subtypes of KRAS were G12C, G12D, and G12V In the KRAS mutation group, the highest mutation frequency other than KRAS was TP53, followed by STK11 and KMT2C. We found that among patients received immunotherapy, KRAS-mutant patients were more sensitive to immunotherapy, with an objective response rate (ORR) of 65% and a disease control rate (DCR) of 80%. Survival analysis found that patients with KRAS mutation had better prognosis with immunotherapy than the non-KRAS mutation patients by comparing the overall survival (OS) (median OS: 18.1 months vs 12.2 months, p=0.0032) and progression-free survival (PFS) (media PFS: 7.9 months vs 3.6 months, p=0.01). We found that the patients with KRAS mutation had better prognosis with immunotherapy than with chemotherapy (median OS: 18.1 months vs 12.3 months, p=0.039, PFS 7.9 months vs 4.1 months, p=0.001). Patients with the KRAS G12C mutation had better results with immunotherapy than chemotherapy, but there was no significant difference in outcome between the two groups (OS: p=0.26 PFS: p=0.055). KRAS and TP53 co-mutation and KRAS and KMT2C co-mutation may improve response to immunotherapy. Conclusion: Our results suggested that the gene mutation profile of NSCLC in KRAS mutation group and non-KRAS mutation group were different. The patients with KRAS mutation will have better prognosis with immunotherapy. Keywords: NSCLC, KRAS, mutation, immunotherapy, prognosis