Li Ping, Yang Xuexi, Liu Qin, Zhang Hanchao, Luo Zhumei
Department of Oncology, The Third People's Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, China.
Department of Human Anatomy, School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, China.
Discov Oncol. 2025 May 25;16(1):924. doi: 10.1007/s12672-025-02754-2.
Bladder cancer (BC) is a common and lethal condition that presents a considerable risk to public health. Studies have demonstrated that inflammation is pivotal in the onset and advancement of BC. Pyroptosis is a type of programmed cell death distinguished by inflammatory reactions associated with innate immunity. Inhibiting inflammatory cytokine production and modulating pyroptosis-related pathways may provide a potential treatment approach for BC. We predicted and validated the Pyroptosis-related genes and potential biomarkers associated with BC, ultimately predicting therapeutic drugs based on the hub gene targets.
The gene expression profiles for BC were acquired from the Gene Expression Omnibus (GEO) database. Bioinformatics analysis identified gene expression differences associated with pyroptosis in BC. The differently regulated pyroptosis-related genes were validated, and enrichment studies of specific biological processes and associated signaling pathways in BC were performed. Immune infiltration analysis and single-cell analysis were conducted to clarify the immune infiltration characteristics in BC. Therapeutic agents were forecasted based on critical gene targets.
In BC, 27 differentially expressed pyroptosis-related genes were discovered, with CASP8, NLRP3, CASP3, IL18, TP53, GSDME, IL1A, PYCARD, CYCS, and CASP9 recognized as key genes. Enrichment analysis revealed that the occurrence of pyroptosis was primarily associated with inflammation, activation of immune responses, and apoptosis. Additionally, data validation demonstrated that CASP8, NLRP3, CASP3, IL18, TP53, CYCS, and CASP9 were involved in the regulation of pyroptosis. The results of immune infiltration and single-cell analyses further validated that B-cells-memory, T-cells_CD8, T-cells_follicular-helper, Macrophages-M1, Dendritic_cells_activated, and Mast_cells_resting play significant roles in the immune processes of BC. The drug targeting predictions for pivotal genes identified Triethyl phosphate, Regorafenib, Ponatinib, Lenvatinib, Nintedanib, and Quercetin as potential key drugs or compounds for the treatment of BC.
This study elucidated the relationship between the development of BC and mechanisms of cellular senescence, apoptosis, and immunity. It clarified the roles of 27 genes associated with cellular senescence in BC and predicted that Triethyl phosphate, Regorafenib, Ponatinib, Lenvatinib, Nintedanib, and Quercetin may be key drugs or compounds for the treatment of BC.
膀胱癌（BC）是一种常见且致命的疾病，对公众健康构成重大风险。研究表明，炎症在膀胱癌的发生和发展中起关键作用。细胞焦亡是一种程序性细胞死亡，其特征在于与先天免疫相关的炎症反应。抑制炎性细胞因子的产生并调节细胞焦亡相关途径可能为膀胱癌提供一种潜在的治疗方法。我们预测并验证了与膀胱癌相关的细胞焦亡相关基因和潜在生物标志物，最终基于枢纽基因靶点预测治疗药物。
从基因表达综合数据库（GEO）获取膀胱癌的基因表达谱。生物信息学分析确定了与膀胱癌中细胞焦亡相关的基因表达差异。对差异调节的细胞焦亡相关基因进行了验证，并对膀胱癌中特定生物学过程和相关信号通路进行了富集研究。进行了免疫浸润分析和单细胞分析以阐明膀胱癌中的免疫浸润特征。基于关键基因靶点预测治疗药物。
在膀胱癌中，发现了27个差异表达的细胞焦亡相关基因，其中半胱天冬酶8（CASP8）、NLR家族含pyrin结构域蛋白3（NLRP3）、半胱天冬酶3（CASP3）、白细胞介素18（IL18）、肿瘤蛋白p53（TP53）、Gasdermin E（GSDME）、白细胞介素1α（IL1A）、凋亡相关斑点样蛋白（PYCARD）、细胞色素c（CYCS）和半胱天冬酶9（CASP9）被识别为关键基因。富集分析表明，细胞焦亡的发生主要与炎症、免疫反应激活和细胞凋亡有关。此外，数据验证表明CASP8、NLRP3、CASP3、IL18、TP53、CYCS和CASP9参与了细胞焦亡的调节。免疫浸润和单细胞分析结果进一步验证了记忆B细胞、细胞毒性T细胞、滤泡辅助性T细胞、M1型巨噬细胞、活化树突状细胞和静息肥大细胞在膀胱癌免疫过程中发挥重要作用。对关键基因的药物靶向预测确定磷酸三乙酯、瑞戈非尼、波纳替尼、乐伐替尼、尼达尼布和槲皮素为治疗膀胱癌的潜在关键药物或化合物。
本研究阐明了膀胱癌发生与细胞衰老、凋亡和免疫机制之间的关系。明确了27个与细胞衰老相关基因在膀胱癌中的作用，并预测磷酸三乙酯、瑞戈非尼、波纳替尼、乐伐替尼、尼达尼布和槲皮素可能是治疗膀胱癌的关键药物或化合物。
