Glypican-1 in Rhabdomyosarcoma: A Multi-omics Exploration of a Targetable Biomarker.

INTRODUCTION: Glypican-1 (GPC1), a heparan sulfate proteoglycan found on the cell surface, has been associated with carcinogenesis and chemoresistance in several malignancies. However, its function in rhabdomyosarcoma remains poorly understood. METHODS: GPC1 protein expression was evaluated in rhabdomyosarcoma tissue microarrays using immunohistochemistry and quantified using the Allred scoring system. Transcriptomic analysis was performed using the GSE108022 dataset, and protein-protein interaction networks were analyzed using STRING. Structural features were assessed using AlphaFold, and drug sensitivity associations were explored using CTRP data. RESULTS: GPC1 protein expression was detected in 61.5% (64/104) of rhabdomyosarcoma cases, while 75% of normal skeletal muscle samples were negative. A significant association was observed between GPC1 expression and tumor subtype (p = 0.002, Cramér's V = 0.403), as well as sex (p = 0.025, Cra-mér's V = 0.219). Transcriptomic analysis showed significantly higher GPC1 expression in rhabdomyosarcoma compared to normal muscle (p < 0.001). Protein interaction analysis revealed enrichment in pathways related to cell adhesion, growth factor signaling, and extracellular matrix organization. Drug-sensitivity analysis indicated that higher GPC1 expression was associated with resistance to PI3K and HDAC inhibitors and increased sensitivity to vincristine, topotecan, and alisertib. DISCUSSION: GPC1 is aberrantly expressed in rhabdomyosarcoma, influencing neoplastic signaling and treatment responses, and new patents emphasize its potential for therapeutic targeting and diagnostic purposes Conclusion: GPC1 is aberrantly overexpressed, readily accessible to ligands or other molecules, and is a functionally significant biomarker in rhabdomyosarcoma, with emerging potential for diagnostic purposes and targeted therapy development.