Proteogenomic characterization unveils biomarkers associated with chemoresistance in muscle-invasive bladder cancer.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40749681.
- Also identified by DOI 10.1016/j.xcrm.2025.102255 and PMC identifier 12432383.
- Licence recorded as CC BY-NC-ND.
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Abstract
To explore potential chemoresistance mechanisms and identify therapeutic opportunities in muscle-invasive bladder cancer (MIBC), we conduct comprehensive proteogenomic characterization of 46 pre- and 14 post-treatment MIBC tumors incorporating genomics, transcriptomics, proteomics, and phosphoproteomics. Multi-omics clustering not only recapitulated established molecular subtypes but also revealed subtypes associated with chemotherapy sensitivity. Protein isoform level analysis identifies protein abundance of a short isoform of ATAD1 and RAF family proteins as biomarkers of chemosensitivity. Integration of proteomic and phosphoproteomic data reveals Wnt signaling via GSK3B-S9 phosphorylation and the JAK/STAT pathway as potential targets to overcome chemoresistance. Correlations between PD-L1 and TROP-2/NECTIN-4 indicate an additive benefit of combination therapy targeting these proteins. Overall, this study serves as a valuable resource for researchers and clinicians aiming to better understand and treat chemoresistant MIBC.
Medical subject headings
- Urinary Bladder Neoplasms
- Drug Resistance, Neoplasm
- Biomarkers, Tumor
- Proteogenomics