Characteristics of Met gene and its relationship with immune index TMB/MMR genes/DDR genes in Chinese NSCLC population.

Abstract

147 Background: Patients with driver gene mutations in NSCLC can benefit significantly from corresponding targeted therapy, but respond poorly to immunotherapy (such as EGFR, ALK). As a driver gene of NSCLC, the relationship between the characteristics of Met and many immune indicators in the Chinese population is still unclear. This study aims to elucidate the characteristics of the Met gene and its relationship with immune indicators in the Chinese NSCLC population. Methods: 732 Formalin-Fixed Paraffin-Embedded (FFPE) lung adenocarcinoma samples were collected and detected by Next Generation Sequencing 603-gene panel from July 31, 2021 to March 14, 2023 were selected from the study. The biomarkers of immunotherapy (TMB-High [≥10/Mb], MSI-High, and PD-L1 22C3 [TPS], DDR-related genes (ATM, ATR, BRCA1, BRCA2, BRIP1, CHEK1, CHEK2, FANCA, MRE11, PALB2, RAD50, RAD51C, RAD51D) and MMR-related genes (MLH1, MSH2, MSH6, PMS2) were also calculated. Results: Among the 732 subjects included in the previous detection, a total of 32 cases were detected to carry Met-related gene mutations. The detection rate of Met gene was 4.37%, which was consistent with the mutation probability of Met mutation of 4-6% in previous studies. The median age was 65 (13-97). 81% of patients belonged to mutations of unknown clinical significance (26/32); 15% of patients belonged to exon 14 skipping type (5/32); Met amplification accounted for the least, accounting for only 6% (2/32 ). The top 3 loci of mutation frequency were Met_L221W (4/32), MET_Q1067K (2/32), and MET_F206S (2/32). The gene partners of Met co-mutation were analyzed, and the top five genes were PPP2R1A, HIST1H3G, CDKN1B, SYK, and ERBB4. In the analysis of the immune indicators of the Met mutant population and the Met wild-type population, the Mann-Whitney U test found that among the TMB indicators, the mean value of the Met group was 8.09 with a standard deviation of 7.91, and the mean value of the un-Met group was 5.94 with a standard deviation of 4.98. Met was correlated with TMB with statistical difference (P value 0.02). Among the MSI indicators, the mean value of the Met group was 8.16, and the mean value of the un-Met group was 7.76. The correlation between Met and MSI status was not significant. We also paid attention to Met and DDR-related genes and MMR-related genes. Mann-Whitney U analysis showed that there was no significant correlation between MET group and wild-type MET group and DDR gene (p-value: 1.0), but there was a significant relationship between MET group and wild-type MET group and MMR gene (p-value: 0.026). Conclusions: In the Chinese NSCLC population, there is a correlation between Met expression and TMB, and the Met mutation will increase the TMB value. Met expression was significantly correlated with MMR-related gene mutations.