Transcriptomic Analysis of Children/Adolescents and Young Adults Versus Adult Synovial Sarcomas Reveals Age-Related...

Synovial sarcoma (SS) is a rare malignancy, accounting for 5%-10% of all soft tissue sarcomas, and characterized by the SS18::SSX translocation. SS predominantly affects young individuals, with a peak incidence in the fourth decade of life. Children (<15 years), and adolescents and young adults (AYAs; 15-29 years) with SS tend to have better survival rates than older adults; however, the biological basis for these age-related differences remains poorly understood.

In this study, high-throughput RNA sequencing (RNA-seq) was used to investigate biological differences in SS across age groups. Transcriptomic profiles of primary tumor tissues from 14 patients younger than 29 years were compared with those from 8 adult patients (>29 years), with the aim of identifying age-related molecular features of SS. In addition, enrichment of recently described transcriptional signatures associated with SS tumor components and infiltrating cell populations was evaluated in our dataset.

RNA-seq analysis identified differential expression of RPL39 and GATA3 between children/AYA and adult patients. Immunohistochemical analysis confirmed increased GATA3 expression in adult tumors. Comparative analyses based on SS-related transcriptional signatures further demonstrated enrichment of actively cycling tumor cells in adult samples, as well as a trend toward increased M2 macrophage infiltration in approximately half of the children/AYA samples.

This study reveals age-related molecular and tumor microenvironment differences in SS that may contribute to disparities in clinical outcomes. These findings underscore the need for further studies to validate these results and to support the development of age-tailored therapeutic strategies.