Integrated pan-cancer analysis and experimental validation reveal that syndecan-1 drives glioblastoma pathogenesis and associates with immune infiltration.

BACKGROUNDS: Syndecan-1 (SDC1) is a key transmembrane proteoglycan involved in cell adhesion and epithelial integrity. Although evidence links SDC1 to tumor progression, its pan-cancer functions and mechanistic roles are not fully understood.

METHODS

We defined the multidimensional role of SDC1 across cancers by leveraging multi-platform genomic and clinical data. Our study characterized its associations with patient survival, molecular mechanisms, immune contexture, and therapeutic sensitivity. Initial observations in glioma subtypessuggested a pro-tumorigenic function. Consequently, this functional role in glioblastoma (GBM) was empirically validated through a combination of cellular-level assays and animal xenograft models.

RESULTS

SDC1 expression was upregulated in numerous cancer types, correlating with poorer survival rates among patients. Receiver operating characteristic (ROC) analyses confirmed its robust diagnostic value across malignancies. Notably, a notable correlation was identified between SDC1 levels and key components within the tumor microenvironment, including CD4+/CD8 + T lymphocytes, cancer-associated fibroblasts (CAFs), and myeloid-derived suppressor cells (MDSCs). Functional assays revealed that SDC1 depletion markedly attenuated GBM cell proliferation and migration. Subsequently, the capacity for migration and tissue invasion was assessed using both experimental and animal model systems.

CONCLUSION

Integrated bioinformatic and experimental analyses identify SDC1 as a pan-cancer biomarker with particular clinical significance in GBM. Its expression correlates with immune infiltration patterns, positioning SDC1 as a promising diagnostic and immunotherapeutic target.