Age-Stratified Transcriptomic Profiling Reveals Biologically Distinct Molecular Phenotypes Across Pediatric,...

Area of Science:

• Oncology
• Genomics
• Transcriptomics

Background:

• Osteosarcoma presents different clinical behaviors in pediatric versus adult patients.
• Genomic data suggests age-related molecular differences, but transcriptomic characterization is limited.
• This study addresses the need for age-specific transcriptomic analysis in osteosarcoma.

Purpose of the Study:

• To identify age-associated transcriptional differences in osteosarcoma.
• To develop a prognostic signature specific to pediatric osteosarcoma.
• To understand the distinct biological profiles of pediatric, adolescent, and adult osteosarcoma.

Main Methods:

• Bulk RNA sequencing of 70 osteosarcoma tumor specimens stratified by age (pediatric, adolescent, adult).
• Differential gene expression, functional enrichment, and immune infiltration analyses were performed.
• A pediatric-specific 10-gene signature was developed and validated using the TARGET-OS cohort.

Main Results:

• Pediatric osteosarcoma displayed a hyperproliferative phenotype with enriched cell cycle pathways.
• Adolescent tumors showed immune-inflammatory signatures and active immune infiltration, unlike pediatric and adult tumors.
• A 10-gene pediatric signature correlated with inferior overall and progression-free survival, validated in an independent cohort.

Conclusions:

• Distinct transcriptional profiles define pediatric, adolescent, and adult osteosarcoma as biologically different entities.
• The identified 10-gene signature serves as a potential biomarker for risk stratification in pediatric osteosarcoma.
• These findings support the development of age-adapted therapeutic strategies for osteosarcoma.