Incidence and PD-L1 Expression of MET 14 Skipping in Chinese Population: A Non-Selective NSCLC Cohort Study Using RNA-Based Sequencing

Background: Mesenchymal–epithelial transition ( MET ) exon14 skipping mutations represent a clinically unique molecular subtype of NSCLC. The prevalence rates of MET exon 14 skipping in lung adenocarcinoma (ADC) range from 0.9% to 4.0% in Asian populations. Since some somatic variants that do not encompass the MET exon 14 splice sites might also induce MET exon 14 skipping, the RNA-based sequencing is speculated as the most accurate method for detecting exon 14 skipping. Patients and Methods: A total of 951 NSCLC patients from two hospitals were enrolled in this study. MET exon14 skipping was detected using RNA-based next-generation sequencing (NGS). Also, immunohistochemistry (IHC) was performed in 405 samples simultaneously. Results: The overall estimated prevalence of MET exon 14 skipping was approximately 1.8% in ADCs and 1.7% in NSCLCs. The detection rate of MET exon 14 skipping from surgical resection specimen was 2.3% in NSCLCs and 2.0% in ADCs. The MET exon 14 skipping was identified in 6.6% of EGFR / KRAS / ALK / ROS1 / RET -negative ADCs. Additionally, PD-L1 was found to be highly expressed in NSCLC patients harboring MET exon 14 skipping ( P < 0.01). Conclusion: The prevalence of MET exon14 skipping in lung ADCs in the East Asian population was similar to that of the Western population as assessed by RNA-based NGS. The NSCLC patients with MET exon 14 skipping were older than those with other oncogenic driver mutations, such as EGFR, ALK , and ROS1 . In addition, PD-L1 was highly expressed in NSCLC patients with MET exon 14 skipping.