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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1573412
This article is part of the Research TopicInnovative Therapeutic Approaches for Complex Cancers: Exploring New Strategies in Glioblastoma, Urogenital, and Bladder CancersView all 9 articles
Identification of SCAMP2 as a Regulator of NOTCH Signaling in Cisplatin Resistance through a Novel Prognostic Model for Bladder Cancer
Provisionally accepted
Long Jun Cai1
Shaoqi Zhang1
Fangfang Zheng1Furong Ji1
Jin Wang2Long Shi1Liu Chao1
Xiangyu Wang1Jianjun Zhang1Zhiyong Chen3*- 1Suqian Hospital Affiliated to Xuzhou Medical University, Suqian, Jiangsu Province, China
- 2Soochow University, Suzhou, China
- 3The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China
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Bladder cancer remains a formidable challenge in clinical oncology, particularly due to the emergence of platinum resistance, which significantly compromises patient outcomes. Despite extensive efforts to develop effective prognostic models, their clinical utility has often been limited. In this study, we employed a robust statistical approach, LASSO-COX regression analysis, to construct a novel prognostic model for bladder cancer based on cisplatin sensitivity-related genes (CSRGs). Our model was validated using the TCGA-BLCA dataset and an independent validation set, GSE32894, demonstrating superior predictive performance with high AUC values. We identified SCAMP2 as a pivotal gene with elevated expression in bladder cancer, strongly correlated with sensitivity to various anti-cancer drugs, including cisplatin. To further explore the biological function of SCAMP2, we conducted CCK-8 and EdU assays to assess cell proliferation, transwell assays for cell migration, and flow cytometry to evaluate apoptosis. Our results revealed that SCAMP2 mediates drug resistance in bladder cancer cells through the NOTCH signaling pathway, underscoring its role in the molecular mechanisms underlying chemotherapy resistance. Further in vivo experiments also demonstrated that SCAMP2 overexpression significantly enhanced cisplatin sensitivity in bladder cancer tissues. These findings highlight the significance of CSRGs and SCAMP2 in improving bladder cancer prognosis and guiding personalized treatment strategies, offering valuable insights into potential therapeutic targets for overcoming drug resistance.
Keywords: cisplatin sensitivity, Prognostic model, Bladder cancer, SCAMP2, Notch pathway
Received: 09 Feb 2025; Accepted: 14 Apr 2025.
Copyright: © 2025 Cai, Zhang, Zheng, Ji, Wang, Shi, Chao, Wang, Zhang and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Zhiyong Chen, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.