{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:03:21Z","timestamp":1753891401342,"version":"3.41.2"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Bladder cancer remains a major challenge in clinical oncology, particularly due to the development of platinum resistance, which severely impacts patient prognosis. Despite numerous attempts to create effective prognostic models, their clinical applicability has often been limited.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we utilized a robust statistical approach, LASSO-COX regression analysis, to develop a novel prognostic model for bladder cancer based on cisplatin sensitivity-related genes (CSRGs). The model was validated using both the TCGA-BLCA dataset and an independent validation set, GSE32894. Additionally, we employed various <jats:italic>in vitro<\/jats:italic> assays, including CCK-8 and EdU assays for cell proliferation, transwell assays for migration, and flow cytometry for apoptosis analysis, to investigate the biological function of the identified genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our prognostic model demonstrated superior predictive performance, with high AUC values. SCAMP2 was identified as a critical gene with elevated expression in bladder cancer, showing strong correlation with sensitivity to multiple anti-cancer drugs, including cisplatin. Further functional assays revealed that SCAMP2 mediates drug resistance in bladder cancer cells via the NOTCH signaling pathway. Additionally, <jats:italic>in vivo<\/jats:italic> experiments showed that SCAMP2 overexpression significantly enhanced cisplatin sensitivity in bladder cancer tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These findings underscore the potential of CSRGs, particularly SCAMP2, as critical biomarkers for bladder cancer prognosis. The identification of SCAMP2 as a regulator of NOTCH signaling in cisplatin resistance offers new insights into the molecular mechanisms of chemotherapy resistance and suggests potential therapeutic targets for overcoming drug resistance. Our model could guide personalized treatment strategies and improve bladder cancer patient outcomes.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1573412","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T05:27:06Z","timestamp":1746682026000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of SCAMP2 as a regulator of NOTCH signaling in cisplatin resistance through a novel prognostic model for bladder cancer"],"prefix":"10.3389","volume":"16","author":[{"given":"Longjun","family":"Cai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaoqi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangfang","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Furong","family":"Ji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Long","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liu","family":"Chao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianjun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiyong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,8]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"B2","article-title":"Outpatient photodynamic diagnosis-guided laser destruction of bladder tumors is as good as conventional inpatient photodynamic diagnosis-guided transurethral tumor resection in patients with recurrent intermediate-risk low-grade ta bladder tumors","volume":"83","author":"Pedersen","year":"2023","journal-title":"A Prospective Randomized Noninferiority Clin Trial. 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