二硫代磷人病是一种由二硫化物应激引起的新型细胞死亡，其依赖于半胱氨酸二硫化物的积累，导致细胞毒性和细胞死亡的触发。然而，二硫代磷人病相关基因在膀胱尿路上皮癌（BLCA）中的直接预后影响和调控机制尚不清楚。为了探究10个二硫代磷人病相关基因的作用，对这10个基因的多组学数据进行了全面分析。接下来，基于七个二硫代磷人病相关的差异表达基因，开发了一个新的二硫代磷人病相关基因评分，用于帮助预测BLCA的预后。使用免疫组化、EDU、实时PCR和免疫印迹验证了该模型。高风险评分组和低风险评分组之间存在显著的功能差异，风险评分较高的样本表现出较高的恶性程度。此外，高风险评分组的肿瘤排斥和肿瘤免疫功能障碍与排斥评分都高于低风险评分组。风险评分与免疫检查点的表达呈正相关。药物敏感性分析显示，低风险评分组对顺铂、多柔比星、多西他赛和吉西他滨的敏感性高于高风险评分组。此外，TM4SF1的表达与BLCA的恶性程度呈正相关，敲除TM4SF1后，BLCA细胞的增殖能力减弱。本研究结果表明，二硫代磷人病相关基因通过参与免疫细胞浸润影响BLCA的预后。因此，这些发现表明了二硫代磷人病在BLCA中的作用及其潜在调控机制。© 2023. 作者，在Springer-Verlag GmbH Germany的独家许可下，Springer Nature的一部分。

Disulfidptosis is a novel type of cell death induced by disulphide stress that depends on the accumulation of cystine disulphide, causing cytotoxicity and triggering cell death. However, the direct prognostic effect and regulatory mechanism of disulfidptosis-related genes in bladder urothelial carcinoma (BLCA) remain unclear.To explore the role of 10 disulfidptosis-related genes, the multiomic data of 10 genes were comprehensively analysed. Next, based on seven disulfidptosis-related differentially expressed genes, a novel disulfidptosis-related gene score was developed to help predict the prognosis of BLCA. Immunohistochemistry, EDU, Real-time PCR and western blot were used to verify the model.Significant functional differences were found between the high- and low-risk score groups, and samples with a higher risk score were more malignant. Furthermore, the tumour exclusion and Tumour Immune Dysfunction and Exclusion scores of the high-risk score group were higher than those of the low-risk score group. The risk score was positively correlated with the expression of immune checkpoints. Drug sensitivity analyses revealed that the low-risk score group had a higher sensitivity to cisplatin, doxorubicin, docetaxel and gemcitabine than the high-risk score group. Moreover, the expression of the TM4SF1 was positively correlated with the malignancy degree of BLCA, and the proliferation ability of BLCA cells was reduced after knockdown TM4SF1.The present study results suggest that disulfidptosis-related genes influence the prognosis of BLCA through their involvement in immune cell infiltration. Thus, these findings indicate the role of disulfidptosis in BLCA and its potential regulatory mechanisms.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.