Age-stratified transcriptomic profiling reveals biologically distinct molecular phenotypes across pediatric, adolescent, and adult osteosarcoma

Osteosarcoma exhibits a bimodal age distribution with distinct clinical behaviors between pediatric and adult patients. In this study, bulk RNA sequencing was performed on tumor specimens from 70 osteosarcoma patients stratified into pediatric (14 years and younger), adolescent (15 to 18 years), and adult (19 years and older) groups. Differential expression, functional enrichment, and immune infiltration analyses were conducted to characterize age-associated transcriptional differences. Pediatric tumors exhibited a hyperproliferative phenotype, adolescent tumors showed enhanced immune-related signatures, and adult tumors displayed activation of osteogenic differentiation programs. A characteristic pediatric-specific gene signature was further identified, providing insights into age-related molecular heterogeneity in osteosarcoma.