膀胱癌（BLCA）是一种发病率高、缺乏特定生物标记和药物靶点的泌尿系癌症。免疫原性细胞死亡（ICD）被归类为一种受调控的细胞死亡方式，越来越多的证据表明，ICD 可以重塑肿瘤的免疫微环境，有助于免疫治疗策略的开发。本研究的目的是揭示 ICD 在膀胱癌中的特定机制，并进一步预测治疗预后。通过共识聚类分析，将 TCGA 数据库中的膀胱癌患者分成不同的 ICD 亚型。此外，我们开发了一个 ICD 计分系统，并构建了基于 ICD 得分的风险签名和诊断模型以更好地表征患者。此外，我们进行了一系列的实验来验证相关发现。基于 ICD 相关基因的转录组表达水平，共有 403 名 BLCA 患者被分成了两个亚组，其 ICD 分子模式不同。这些亚组显示出不同的临床病理特征、存活结果、肿瘤微环境特征、免疫相关得分和治疗反应。此外，建立的预测模型和 ICD 分数可以有效地区分高风险/高得分患者和低风险/低得分患者，具有良好的预测价值。最后，我们发现关键基因 HSP90AA1 在高 ICD 得分组和膀胱癌组织中高表达，并证实与膀胱癌细胞增殖有关。总之，我们基于 ICD 相关基因建立了一种新的膀胱癌分类系统。这种分层具有显著的预测临床结果的能力，可以有效地评估 BLCA 患者的预后和免疫治疗。最后，我们证实 HSP90AA1 在 BLCA 中高表达，并可作为一个有前途的治疗靶点。©2023年作者，独家许可授予西班牙肿瘤学联合会（FESEO）。

Bladder cancer (BLCA) is defined as a type of urinary cancer with high incidence and lack of specific biomarkers and drug targets. Immunogenic cell death (ICD) has been classified as a regulated type of cell death. Growing evidence suggested that ICD can reshape the tumor immune microenvironment, which may contribute to the development of immunotherapy strategies. The aim of this study was to reveal the specific mechanism of ICD in bladder cancer and to further predict the prognostic immunotherapy outcomes.By consensus clustering analysis, bladder cancer patients in TCGA database were divided into different ICD subtypes. Additionally, we developed an ICD-scoring system and constructed the ICD score-based risk signature and nomogram to better characterize patients. Furthermore, we carried out a series of experiments to verify the relevant findings.Based on the transcriptome expression levels of ICD-related genes, a total of 403 BLCA patients in the TCGA database were divided into two subgroups with different ICD molecular patterns by consensus cluster analysis. These subgroups showed different clinicopathological features, survival outcomes, tumor microenvironment (TME) characteristics, immune-related scores, and treatment response. Moreover, the established prediction model and ICD score can effectively distinguish high risk/score patients from low risk/score patients, which has excellent predictive value. Finally, we found that the key gene HSP90AA1 was highly expressed in the high-ICD score group and in bladder cancer tissues, and was confirmed to be associated with the proliferation of bladder cancer cells.To sum up, we established a new classification system for BLCA based on ICD-related genes. This stratification has significant predictive power for clinical outcomes and can effectively evaluate the prognosis and immunotherapy of BLCA patients. Finally, it was proved that HSP90AA1 was highly expressed in BLCA and would be a promising therapeutic target for BLCA.© 2023. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).