Distinct and Convergent Roles of the Synovial Sarcoma X Breakpoint Family of Cancer-Testis Antigens in Ovarian Cancer

Ovarian cancer (OC) is a leading cause of death in women, with limited advances in diagnosis and treatment over the past decade. The Synovial Sarcoma, X Breakpoint (SSX) family of cancer-testis antigens represent promising biomarkers and immunotherapeutic targets; however, the functions of individual SSX family members remain poorly defined due to their high sequence similarity. We investigated the roles of SSX2A, SSX2B and SSX3 using RNA sequencing, in vitro and in vivo assays. Pathway analysis revealed involvement in nucleosome assembly, calcium signalling, and cellular stress responses, alongside increased OC cell proliferation in vitro following overexpression. Additionally, SSX variants altered key epithelial–mesenchymal transition (EMT) associated markers, including upregulation of the transcription factor, SLUG. Integration with patient transcriptomic datasets identified several SSX regulated genes associated with overall survival (OS). These findings suggest that SSX family members are not functionally redundant and may contribute to OC progression and clinical outcome.