{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T23:05:20Z","timestamp":1793833520812,"version":"4.6.1"},"reference-count":66,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":146,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    At the transcriptomic level, several molecular subtyping schemes have been established to elucidate the intrinsic heterogeneity of urothelial carcinoma and to inform prognostic assessment and therapeutic guidance. However, a unified molecular classification scheme characterizing genomic alterations is lacking. Unsupervised and supervised clustering identified two distinct mutational signature subtypes. Kaplan\u2013Meier analysis demonstrated that patients with the MUT2 subtype had a higher risk of death than those with the MUT1 subtype across multiple cohorts, including IMvigor210 (hazard ratio [HR], 1.74; 95% confidence interval [CI], 1.27\u20132.37;\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.001), UC\u2010GENOME (HR, 1.54; 95% CI, 0.93\u20132.54;\n                    <jats:italic>p<\/jats:italic>\n                    = 0.091), The Cancer Genome Atlas (TCGA; HR, 1.45; 95% CI, 1.06\u20131.98;\n                    <jats:italic>p<\/jats:italic>\n                    = 0.020), MSK2022 (HR, 1.34; 95% CI, 1.10\u20131.64;\n                    <jats:italic>p<\/jats:italic>\n                    = 0.004), MSK2015 (HR, 3.43; 95% CI, 1.36\u20138.64;\n                    <jats:italic>p<\/jats:italic>\n                    = 0.005), and the Tongji cohort (HR, 4.99; 95% CI, 0.57\u201343.69;\n                    <jats:italic>p<\/jats:italic>\n                    = 0.11). Immunotherapy response rates were significantly higher in the MUT1 subtype than in the MUT2 subtype in IMvigor210 (31.8% vs. 13.1%;\n                    <jats:italic>p<\/jats:italic>\n                    = 0.003) and UC\u2010GENOME (42.3% vs. 29.0%;\n                    <jats:italic>p<\/jats:italic>\n                    = 0.022). Consistent with these findings, single\u2010cell analysis showed that MUT2 tumors were enriched in tumor\u2010associated fibroblast subpopulations and had a lower abundance of immune effector cells. Overall, this genomic analysis identified two mutation\u2010based subtypes of urothelial carcinoma associated with patient prognosis and immunotherapy response.\n                  <\/jats:p>","DOI":"10.1155\/humu\/2797474","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T11:13:47Z","timestamp":1779880427000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrated Genomic and Single\u2010Cell Analysis Reveals Heterogeneity, Prognosis, and Treatment Vulnerability in Urothelial 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