Proteogenomic Characterization of Bladder Cancer Reveals Sensitivity to Apoptosis Induced by Tumor Necrosis Factor–related Apoptosis-inducing Ligand in FGFR3-mutated Tumors

作者：Clarice S. Groeneveld, Virginia Sánchez‐Quiles, Florent Dufour, Mingjun Shi, Florent Dingli, Rémy Nicolle, Elodie Chapeaublanc, Patrick Poullet, Daniel Jeffery, Clémentine Krucker, Pascale Maillé, Francis Vacherot, Dimitri Vordos, Simone Benhamou, Thierry Lebrét, Olivier Micheau, Andreï Zinovyev, Damarys Loew, Yves Allory, Aurélien de Reyniès, Isabelle Bernard‐Pierrot, François Radvanyi · 发表于：European Urology · 年份：2023 · DOI：10.1016/j.eururo.2023.05.037 · 被引用次数：30 · 研究领域：Fibroblast Growth Factor Research、Bladder and Urothelial Cancer Treatments、Proteoglycans and glycosaminoglycans research

BACKGROUND: Molecular understanding of muscle-invasive (MIBC) and non-muscle-invasive (NMIBC) bladder cancer is currently based primarily on transcriptomic and genomic analyses. OBJECTIVE: To conduct proteogenomic analyses to gain insights into bladder cancer (BC) heterogeneity and identify underlying processes specific to tumor subgroups and therapeutic outcomes. DESIGN, SETTING, AND PARTICIPANTS: Proteomic data were obtained for 40 MIBC and 23 NMIBC cases for which transcriptomic and genomic data were already available. Four BC-derived cell lines harboring FGFR3 alterations were tested with interventions. INTERVENTION: Recombinant tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), second mitochondrial-derived activator of caspases mimetic (birinapant), pan-FGFR inhibitor (erdafitinib), and FGFR3 knockdown. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Proteomic groups from unsupervised analyses (uPGs) were characterized using clinicopathological, proteomic, genomic, transcriptomic, and pathway enrichment analyses. Additional enrichment analyses were performed for FGFR3-mutated tumors. Treatment effects on cell viability for FGFR3-altered cell lines were evaluated. Synergistic treatment effects were evaluated using the zero interaction potency model. RESULTS AND LIMITATIONS: Five uPGs, covering both NMIBC and MIBC, were identified and bore coarse-grained similarity to transcriptomic subtypes underlying common features of these different entities; uPG-E was ass...