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

Vollständiger Abstract

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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.