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膀胱癌中双硫死亡相关基因的预后预测及免疫治疗综合分析

Prognosis Prediction of Disulfidptosis-Related Genes in Bladder Cancer and a Comprehensive Analysis of Immunotherapy.

作者信息

Jiang Chonghao, Xiao Yonggui, Xu Danping, Huili Youlong, Nie Shiwen, Li Hubo, Guan Xiaohai, Cao Fenghong

机构信息

Affiliated Hospital of North China University of Science and Technology, Tangshan 063000, China.

Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu 61000, China.

出版信息

Crit Rev Eukaryot Gene Expr. 2023;33(6):73-86. doi: 10.1615/CritRevEukaryotGeneExpr.2023048536.

Abstract

As a newly discovered mechanism of cell death, disulfidptosis is expected to help diagnose and treat bladder cancer patients. First, data obtained from public databases were analyzed using bioinformatics techniques. SVA packages were used to combine data from different databases to remove batch effects. Then, the differential analysis and COX regression analysis of ten disulfidptosis-related genes identified four prognostically relevant differentially expressed genes which were subjected to Lasso regression for further screening to obtain model-related genes and output model formulas. The predictive power of the prognostic model was verified and the immunohistochemistry of model-related genes was verified in the HPA database. Pathway enrichment analysis was performed to identify the mechanism of bladder cancer development and progression. The tumor microenvironment and immune cell infiltration of bladder cancer patients with different risk scores were analyzed to personalize treatment. Then, information from the IMvigor210 database was used to predict the responsiveness of different risk patients to immunotherapy. The oncoPredict package was used to predict the sensitivity of patients at different risk to chemotherapy drugs, and its results have some reference value for guiding clinical use. After confirming that our model could reliably predict the prognosis of bladder cancer patients, the risk scores were combined with clinical information to create a nomogram to accurately calculate the patient survival rate. A prognostic model containing three disulfidptosis-related genes (NDUFA11, RPN1, SLC3A2) was constructed. The functional enrichment analysis and immune-related analysis indicated patients in the high-risk group were candidates for immunotherapy. The results of drug susceptibility analysis can guide more accurate treatment for bladder cancer patients and the nomogram can accurately predict patient survival. NDUFA11, RPN1, and SLC3A2 are potential novel biomarkers for the diagnosis and treatment of bladder cancer. The comprehensive analysis of tumor immune profiles indicated that patients in the high-risk group are expected to benefit from immunotherapy.

摘要

作为一种新发现的细胞死亡机制,二硫化物诱导的细胞死亡有望帮助诊断和治疗膀胱癌患者。首先,使用生物信息学技术分析从公共数据库获得的数据。利用SVA软件包合并来自不同数据库的数据以消除批次效应。然后,对10个与二硫化物诱导的细胞死亡相关的基因进行差异分析和COX回归分析,确定了4个与预后相关的差异表达基因,对其进行Lasso回归进一步筛选,以获得模型相关基因并输出模型公式。验证了预后模型的预测能力,并在HPA数据库中验证了模型相关基因的免疫组化结果。进行通路富集分析以确定膀胱癌发生和进展的机制。分析不同风险评分的膀胱癌患者的肿瘤微环境和免疫细胞浸润情况,以实现个性化治疗。然后,利用IMvigor210数据库的信息预测不同风险患者对免疫治疗的反应性。使用oncoPredict软件包预测不同风险患者对化疗药物的敏感性,其结果对指导临床应用具有一定参考价值。在确认我们的模型能够可靠地预测膀胱癌患者的预后后,将风险评分与临床信息相结合,创建列线图以准确计算患者生存率。构建了一个包含3个与二硫化物诱导的细胞死亡相关基因(NDUFA11、RPN1、SLC3A2)的预后模型。功能富集分析和免疫相关分析表明,高风险组患者是免疫治疗的候选者。药物敏感性分析结果可为膀胱癌患者提供更精准的治疗指导,列线图可准确预测患者生存情况。NDUFA11、RPN1和SLC3A2是膀胱癌诊断和治疗的潜在新型生物标志物。肿瘤免疫图谱的综合分析表明,高风险组患者有望从免疫治疗中获益。

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