Clinicopathological and genomic features of early-onset non-small cell lung cancer across age and ethnicity.

Lung cancer in young patients shows a rising incidence and distinct disease biology but remains understudied. We obtained clinical information and somatic mutation data for two large non-small-cell lung cancer (NSCLC) patient cohorts from the cBioPortal database-the China cohort (N = 1948) and the MSK cohort (N = 6220). Additionally, we extracted clinical data from an internal, real-world NSCLC patients (GZSY cohort, N = 3914) spanning the past decade. By comparing clinicopathological and genomic features across age and ethnicities, we systematically characterized the molecular and clinical phenotype of early-onset NSCLC. Young patients were more likely to be female and never smokers, and carried a higher frequency of actionable driver gene mutations, particularly involving EGFR, ALK, ROS1, and ERBB2 genes. In the China cohort, young patients exhibited significantly higher frequencies of EGFR and ERBB2 mutations and a higher rate of concurrent EGFR-TP53 co-mutations. Advanced stage at diagnosis and TP53 mutation status emerged as independent adverse prognostic factors in young patients. Integration of multi-ethnic genomic and clinical data in this study delineates the distinct clinical and molecular landscape of early-onset NSCLC and supports development of age-targeted, precision therapeutic strategies.