Prognostic significance of copper metabolism-related genes as risk markers in bladder urothelial carcinoma.

IF 1.1 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Jiamo Zhang, Houwei Yang, Xuan Zhang, Jiangchuan Chen, Huaming Luo, Changlong Li, Xin Chen
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引用次数: 0

Abstract

Bladder urothelial carcinoma (BLCA), a prevalent malignant neoplasm affecting the human urinary system, is frequently linked with an unfavorable prognosis in a significant proportion of individuals. More effective and sensitive markers are needed to provide a reference for prognostic judgment. We obtained RNA sequencing data and clinical information of individuals from TCGA, and 133 copper metabolism-related genes from literature. Prognostic genes were evaluated by univariate/multivariate Cox regression analysis and LASSO analysis, and a risk-scoring model was established and validated in the GEO dataset. The CIBERSORT method was utilized to explore immune cell infiltration in BLCA individuals. In addition, tumor immune dysfunction and exclusion (TIDE) and immunophenoscore (IPS) were utilized to verify whether the model can foretell the response of BLCA individuals to immunotherapy. We successfully constructed an 8-gene risk scoring model to foretell individuals' overall survival, and the model performed well in TCGA training and GEO validation cohorts. Lastly, a nomogram containing clinical parameters and risk scores was constructed to help individualized result prediction for individuals. Calibration curves demonstrated a high degree of concordance between the observed and projected survival durations, attesting to its exceptional predictive accuracy. Analysis utilizing CIBERSORT unveiled elevated levels of immune cell infiltration in individuals classified as low risk. TIDE and IPS analyses substantiated that low-risk individuals exhibited a more favorable response to immunotherapy. In summary, the model held immense potential for stratifying the risk of survival and guiding tailored treatment approaches for individuals with BLCA, thereby offering valuable insights for personalized therapeutic interventions.

铜代谢相关基因作为膀胱尿路上皮癌风险标志物的预后意义
膀胱尿路上皮癌(BLCA)是影响人类泌尿系统的一种常见恶性肿瘤,相当一部分患者的预后往往不佳。我们需要更有效、更敏感的标记物来为预后判断提供参考。我们从 TCGA 中获得了个体的 RNA 测序数据和临床信息,并从文献中获得了 133 个铜代谢相关基因。通过单变量/多变量Cox回归分析和LASSO分析评估了预后基因,并在GEO数据集中建立和验证了风险评分模型。利用CIBERSORT方法探讨了BLCA患者的免疫细胞浸润情况。此外,我们还利用肿瘤免疫功能障碍与排斥(TIDE)和免疫表观评分(IPS)来验证该模型是否能预测BLCA患者对免疫疗法的反应。我们成功构建了一个8基因风险评分模型来预测个体的总生存期,该模型在TCGA训练队列和GEO验证队列中表现良好。最后,我们还构建了一个包含临床参数和风险评分的提名图,以帮助个体进行个体化结果预测。校准曲线显示,观察到的生存期与预测的生存期高度吻合,证明了其卓越的预测准确性。利用 CIBERSORT 进行的分析显示,被归类为低风险的患者体内免疫细胞浸润水平升高。TIDE和IPS分析证实,低风险患者对免疫疗法的反应更佳。总之,该模型在对BLCA患者的生存风险进行分层和指导量身定制的治疗方法方面具有巨大的潜力,从而为个性化治疗干预提供了宝贵的见解。
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来源期刊
Nucleosides, Nucleotides & Nucleic Acids
Nucleosides, Nucleotides & Nucleic Acids 生物-生化与分子生物学
CiteScore
2.60
自引率
7.70%
发文量
91
审稿时长
6 months
期刊介绍: Nucleosides, Nucleotides & Nucleic Acids publishes research articles, short notices, and concise, critical reviews of related topics that focus on the chemistry and biology of nucleosides, nucleotides, and nucleic acids. Complete with experimental details, this all-inclusive journal emphasizes the synthesis, biological activities, new and improved synthetic methods, and significant observations related to new compounds.
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