Novel molecular subtypes of METex14 non-small cell lung cancer with distinct biological and clinical significance.

ABSTRACT: Not all MET exon 14 skipping (METex14) NSCLC patients benefited from MET inhibitors. We hypothesized an inter-tumoral heterogeneity in METex14 NSCLC. Investigations at genomic and transcriptomic level were conducted in METex14 NSCLC samples from stage I-III and recurrent/metastatic patients as discovery and validation cohort. Four molecular subtypes were discovered. MET-Driven subtype, with the worst prognosis, displayed MET overexpression, enrichment of MET-related pathways, and higher infiltration of fibroblast and regulatory T cells. Immune-Activated subtype having the most idea long-term survival, had higher tertiary lymphoid structures, spatial co-option of PD-L1⁺ cancer cells, and GZMK⁺ CD8⁺ T cell. FGFR- and Bypass-Activated subtypes displayed FGFR2

SUBMITTER: Chen S 

PROVIDER: S-EPMC11282101 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature