为了增强治疗方法，我们利用细胞死亡指标 (CDI) 创建了一种独特的模式来预测膀胱癌 (BLCA) 患者免疫治疗的有效性。使用差异基因表达和生存分析从 TCGA 数据库中识别出 Hub 预后 CDI，涵盖 13 种死亡模式的 763 个基因。采用亚型评估来评估这些基因对 BLCA 患者预后和免疫治疗结果的影响。采用LASSO回归方法识别显着的CDI，同时采用Cox回归和列线图分析探讨CDI对预后的影响。选择CHMP4C和GSDMB作为后续研究的中心基因。随后，对这两个中心基因进行了进一步研究，探讨其与免疫治疗的关联，并分析其潜在的调控网络。亚型分析显示这些CDI与BLCA患者的预后和免疫治疗显着相关。通过建立 lncRNA XIST/NEAT1-CDIs-miR-146a-5p/miR-429 轴来评估 BLCA 的调控网络。免疫组织化学分析显示膀胱癌组织中 CHMP4C 显着上调，这与 BLCA 患者的不良预后密切相关。此外，我们的研究结果提供了令人信服的证据，表明 CHMP4C 通过激活上皮间质转化 (EMT) 途径在促进 BLCA 进展中发挥着关键作用。这些发现强调了 CHMP4C 对 BLCA 患者预后的负面影响，同时也提供了对 CHMP4C 可能参与的致癌机制和免疫治疗的见解。© 2024 作者。由爱思唯尔有限公司出版

To enhance therapeutic approaches, we created a distinctive pattern utilizing the cell demise indicator (CDI) to predict the effectiveness of immunotherapy in individuals with bladder carcinoma (BLCA). Hub prognostic CDIs were identified from the TCGA database using differential gene expression and survival analysis, encompassing 763 genes across 13 death modes. The subtype assessment was employed to evaluate the impact of these genes on the prognosis and immunotherapeutic outcomes in patients with BLCA. The LASSO regression method was used to identify significant CDIs, while Cox regression and nomogram analyses were conducted to explore the impact of CDIs on prognosis. CHMP4C and GSDMB were selected as the hub genes for the following research. Subsequently, These two central genes underwent further investigation to explore their association with immunotherapy, followed by an analysis of their potential regulatory network. Subtype analysis showed that these CDIs were significantly associated with the prognosis and immunotherapy of BLCA patients. The regulatory network in BLCA was evaluated through the establishment of the lncRNA XIST/NEAT1-CDIs-miR-146a-5p/miR-429 axis. Immunohistochemical analysis revealed a significant up-regulation of CHMP4C in bladder cancer tissues, which was strongly associated with an unfavorable prognosis for BLCA patients. Moreover, our findings provide compelling evidence that CHMP4C plays a pivotal role in promoting BLCA progression through the activation of the epithelial-mesenchymal transition (EMT) pathway. These findings highlight the negative impact of CHMP4C on BLCA patient prognosis, while also providing insights into the oncogenic mechanisms and immunotherapy in which CHMP4C may be involved.© 2024 The Authors. Published by Elsevier Ltd.