1393P - Characteristics of MET gene and its relationship with TMB/MMR genes in Chinese NSCLC population

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, 2021 to March, 2023 were selected from the study. The biomarkers of immunotherapy (TMB-High [≥10/Mb], 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 mutations. The detection rate of MET gene was 4.37%. The median age was 65 (13-97). 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 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 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 SD of 7.91, and the mean value of the un-MET group was 5.94 with SD of 4.98. MET was correlated with TMB with statistical difference (P value 0.02).We also paid attention to MET and MMR-related genes. The analysis showed that 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.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.