Molecular epidemiology of the expression of urokinase plasminogen activator receptor-associated protein (uPARAP) in mesenchymal malignancies

IntroductionSarcomas are highly heterogenous and rare malignant tumors derived from mesenchymal cells. The current standard treatments for advanced disease have low response rates and are typically associated with considerable toxicity. The aim of this study was to investigate the expression of a potential novel therapeutic target and its clinical correlation in sarcomas, namely urokinase plasminogen activator receptor-associated protein (uPARAP/Endo180/CD280).Materials and MethodsWe evaluated uPARAP expression in various sarcoma subtypes and in normal tissues using 12 tissue microarrays. Expression was assessed on immunohistochemically stained slides and scored according to staining intensity and the percentage of positive tumor cells. Clinical correlations between uPARAP expression and selected parameters (gender and sample origin) were analyzed using generalized estimating equations, and survival outcomes were evaluated with Kaplan-Meier and log-rank tests.ResultsOur results demonstrated limited uPARAP expression in normal tissues, while high expression was observed in the majority of analyzed sarcoma subtypes, particularly high (more than 80% of highly positive cases) in fibrosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma, malignant peripheral nerve sheath tumor, and various bone sarcomas. Based on the correlation analyses between uPARAP expression and selected clinical parameters or survival outcomes, most subtypes did not show a statistically significant association.ConclusionIn conclusion, this study highlights the potential of uPARAP as an innovative target for targeted treatments, such as novel antibody-drug conjugates in sarcoma.