Multi-omics profiling reveals CDKN2A mutant early-onset lung squamous cell carcinoma with a “hot” tumor immune microenvironment

Background: Early-onset lung squamous cell carcinoma (LUSC) is a rare and poorly characterized entity. Its distinct clinicopathological, genomic, and tumor immune microenvironment (TIME) profiles remain to be elucidated. This study sought to explore the molecular landscape and immunophenotype of early-onset LUSC, with a focus on uncovering potential genomic associations with its clinical features. Methods: In this retrospective, single-center cohort study, we conducted a comprehensive multi-omics analysis on patients with surgically resected, treatment-naïve early-onset LUSC (subjects aged ≤40 years, n=21) between 2015 and 2024 using whole-exome sequencing (WES) and digital spatial profiling (DSP). To contextualize our findings, we conducted a comparative analysis using publicly available LUSC data from The Cancer Genome Atlas (TCGA) via the Xena platform. Results: group showed a trend toward shorter overall survival (OS). Conclusions: status as a potential biomarker to guide immunotherapy strategies in early-onset LUSC.