Proteomic Profiling of Non-Muscle Invasive Bladder Cancer Reveals Stage-Specific Molecular Signatures and Prognostic Biomarkers

Non-Muscle Invasive Bladder Cancer (NMIBC) includes High-Grade (HG) and Low-Grade (LG) variants, classified by aggressiveness, recurrence risk, and tumor stage—either non-invasive (pTa) or invading the lamina propria (pT1). Cystoscopy is the diagnostic gold standard, with no less invasive alternatives, and the molecular mechanisms driving tumorigenesis and therapy response remain poorly understood. To address this, we conducted a preliminary proteomic study on pTa-LG and pT1-HG NMIBC fresh biopsies at first diagnosis to understand molecular differences and identify potential prognostic biomarkers. Proteomic analysis revealed distinct protein signatures between tumor stages. In pT1-HG, up-regulated proteins were linked to nitric oxide biosynthesis, signal transduction, apoptosis regulation, protein folding, and immune response. PT1-HG down-regulated proteins were involved in cellular localization, cytoskeleton organization, cell adhesion, phagocytosis, and tissue development. Notably, several proteoforms of PDC6I, a protein regulating apoptosis and proliferation, were down-regulated in pT1-HG. Additionally, protein abundance of GANAB, GALE, HNRNPH1, THIC, SEPT8 and MYDGF/C19orf10 was correlated with tumor size, indicating potential as prognostic biomarkers.