Uncovering the prognostic implications and immunological roles of transmembrane protein 208 in bladder cancer by multi omics analysis and experimental verification

In this study, we explored the role of transmembrane protein 208 (TMEM208), a transmembrane protein predominantly located in the endoplasmic reticulum, in bladder cancer (BLCA), where its absence is associated with developmental defects and cellular polarity disorders. Utilizing data from the TCGA database and 15 GEO datasets, we correlated TMEM208 expression with clinical features and employed the ComPPI website and Gene Set Enrichment Analysis (GSEA) to dissect its protein interactions and functional roles. Our analysis revealed that TMEM208 is significantly upregulated in BLCA, positively correlating with clinical severity and poor survival. GSEA indicated associations with oxidative phosphorylation, epithelial-mesenchymal transition, and stemness pathways. Immunoinfiltration analysis showed a predominantly positive correlation with immune cells, except for central memory T cells (Tcm) and T helper cells. Spatial transcriptomics and single-cell sequencing demonstrated TMEM208's predominant expression in tumor cells and fibroblasts, aligning with tumor cell counts, and highlighting its crucial function within the tumor microenvironment. Cellular assays confirmed TMEM208's ability to enhance BLCA cell proliferation, migration, and invasion. In conclusion, TMEM208's overexpression in BLCA suggests its potential as an oncogenic factor, a prognostic indicator of poor outcomes, and a potential therapeutic target.