Cell reports. Medicine · 2025
Proteogenomic characterization unveils biomarkers associated with chemoresistance in muscle-invasive bladder cancer.
СтатьяНазвание и аннотация: Перевод в очереди
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Holt Matthew V, Dou Yongchao, Young Meggie N, Saltzman Alexander B, Anurag Meenakshi, Lei Jonathan T, Jain Antrix, Leng Mei, Kim Beom-Jun, Dobrolecki Lacey E, Faucher Stefanie F, Savage Sara, Wang Chenwei, Shi Zhiao, Villanueva Hugo, Kremers Karoline, Drinnon Kyle D, Castro Patricia D, Ittmann Michael M, Khatani Mehak Mehboob, Kim Sung Han, Ellis Matthew J, Zhang Bing, Malovannaya Anna, Lerner Seth P
Аннотация
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.