The relationship between different subtypes of KRAS and PD-L1 & tumor mutation burden (TMB) based on next-generation sequencing (NGS) detection in Chinese lung cancer patients

Background: KRAS gene mutations are the most common driver oncogenes in non-small cell lung cancer (NSCLC). We conducted an analysis of the immunological characteristics including tumor mutation burden and programmed death-ligand 1 (PD-L1) expression of different subtypes of KRAS in 2880 KRAS-mutant NSCLC patients.

Methods: A total of 2,880 patients with NSCLC were included in the study. Somatic mutation data were provided by Berry Oncology (Fujian, China), Geneplus BioTech (Beijing, China), Nanjing Geneseeq Technology Inc (Nanjing, China), and Burning Rock Biotech (Guangzhou, China). Z-scores were used to unify all data. SPSS 20.0 (SPSS, Chicago, IL, USA) software was used for statistical analyses. All scatter plots and boxplot maps were drawn using GraphPad Prism 8. Tumor mutation burden (TMB) expression was defined by the number of somatic mutations. The PD-L1 clone 22C3 pharmDx kit was used to measure the expression level of PD-L1. Mann-Whitney U test was used for statistical analysis. P value <0.05 was considered statistically significant.

Results: We identified 2,880 patients with KRAS-mutant NSCLC. The percentage level of TMB and expression of PD-L1 was significantly decreased in KRAS Q61X-mutant lung cancer tissue and blood samples (n=162). The percentage level of TMB and expression of PD-L1 in KRAS G13X-mutant lung cancer specimens was significantly increased (n=190).

Conclusions: The findings demonstrate a decreased level of TMB and expression of PD-L1 in KRAS Q61X-mutant lung cancer and the increased level of TMB and expression of PD-L1 in KRAS G13X-mutant lung cancer. Further work is needed to identify if the subtype of KRAS mutation could be a potential therapeutic biomarker in lung cancer patients with KRAS mutation. TMB data was consistently verified in tissue and blood samples and confirmed the feasibility of next-generation sequencing (NGS) verification in plasma samples. Our research may help to provide more individualized treatment options for NSCLC patients.