biostudies-literatureTian YNatural Science Foundation of Liaoning Province (Liaoning Provincial Natural Science Foundation)Department of Education of Liaoning Province (Liaoning Provincial Education Department)National Natural Science Foundation of China (National Science Foundation of China)1976https://www.ebi.ac.uk/biostudies/studies/S-EPMC11861273biostudies-literatureUnknown16(1)Early-onset lung cancer in young adults represents a less studied clinical entity with increasing incidence which still affects a large number of cancer patients. Here we perform a comprehensive analysis of early-onset lung cancer for the clinicopathological features, genomic alterations, gene expression, and immune landscape by establishing a cohort enrolling 421 non-small cell lung cancer (NSCLC) patients from ten medical centers in China. Comparative analysis reveals a distinct genomic alteration between younger and elder patients with NSCLC, with ERBB2 mutations and ALK-rearrangement strikingly more frequent in younger group. Transcriptome profiling indicates altered cellular metabolism and immune-related genes in tumors from younger patients. Immunological analysis reveals a decreasedNature communicationsComprehensive characterization of early-onset lung cancer, in Chinese young adults.PMC118612732020jh2/1030006032470673jczr20200162022jh13/10200026Ma RLu YYu QZhang HZhao WWang HZhang LZhao XWu ZWang RWang SZhou CQi YFei TZhou DWu WLiang RLi PSong CYang BLi RXin HYang XTian YLiu CfalseComprehensive characterization of early-onset lung cancer, in Chinese young adults.Early-onset lung cancer in young adults represents a less studied clinical entity with increasing incidence which still affects a large number of cancer patients. Here we perform a comprehensive analysis of early-onset lung cancer for the clinicopathological features, genomic alterations, gene expression, and immune landscape by establishing a cohort enrolling 421 non-small cell lung cancer (NSCLC) patients from ten medical centers in China. Comparative analysis reveals a distinct genomic alteration between younger and elder patients with NSCLC, with ERBB2 mutations and ALK-rearrangement strikingly more frequent in younger group. Transcriptome profiling indicates altered cellular metabolism and immune-related genes in tumors from younger patients. Immunological analysis reveals a decreased2025-01-01T00:00:00Z2025 Feb2025-04-03T23:35:37.917Z2025-04-03T23:35:37.917ZS-EPMC118612734000063010.1038/s41467-025-57309-4