Longevity & AgingESM1 Drives Bladder Cancer Immune Evasion via the SPP1 Signaling Pathway
A large-scale multi-omics study identified Endothelial cell-specific molecule 1 (ESM1) as significantly overexpressed in bladder cancer tissues at both mRNA and protein levels across 1,558 clinical samples. ESM1 was found to be enriched specifically in lymphatic endothelial cells and activates the SPP1 signaling pathway to promote immune evasion and metastasis. High ESM1 expression suppressed T-cell receptor and Fc gamma R-mediated immune pathways, reduced immune cell infiltration, and increased tumor purity in the tumor microenvironment. Additionally, miR-129-5p was identified as an upstream regulator of ESM1, showing downregulation in bladder cancer and strong early diagnostic performance. ESM1 achieved an AUC of 0.94 for distinguishing cancerous from normal tissue, highlighting its potential as a clinically actionable biomarker.
