Expression and clinical correlations of PRAME in sarcoma subtypes.

Abstract

11067 Background: PRAME (Preferentially Expressed Antigen In Melanoma), a member of the cancer-testis antigen family, has been shown to have increased expression in solid tumors, including sarcoma. PRAME-specific therapies are currently in development for other cancers.Methods: To map the landscape of PRAME expression in sarcoma, we used publicly available data from the Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia (CCLE) and determined which sarcoma subtypes have increased PRAME expression. We also analyzed how PRAME expression correlates with survival and other clinical variables. Furthermore, tumor and normal tissue expression comparisons were performed using data from the Genotype-Tissue Expression (GTEx) project (n = 8,555). Results: PRAME mRNA expression was available for 110 leiomyosarcoma (LMS), 76 undifferentiated pleomorphic sarcoma / myxofibrosarcoma (UPS/MFS), 58 dedifferentiated liposarcoma (DDLPS), 10 synovial sarcoma, 12 malignant peripheral nerve sheath tumor (MPNST), and 57 carcinosarcoma patients in the TCGA and 46 various sarcoma cell lines in the CCLE. We found that PRAME was highly expressed in all synovial sarcomas: the expression in these samples was significantly higher than in LMS, UPS/MFS, and DDLPS (p < 0.001). Furthermore, PRAME also had a significantly higher expression in multifocal LMS compared to non-multifocal LMS (p < 0.05). We did not find any significant difference in survival or in other clinical parameters in these sarcoma subtypes. In uterine carcinosarcoma, PRAME expression was significantly higher than in normal uterus (p < 0.001). In the CCLE cell line data we found that sarcoma subtypes show diverse PRAME expressions, however, all four chondrosarcoma lines have a low expression, which is significantly lower than in Ewing’s sarcoma (p < 0.01), and it shows a similarly lower trend than osteosarcoma (p = 0.0535).Conclusions: To our knowledge this is the first comprehensive analysis of PRAME in multiple sarcoma subtypes. We report statistically significant associations to help guide PRAME specific therapies of sarcoma.