Prognostic analysis of bladder cancer with neddylation-related genes.

IF 2.5 3区生物学

Hereditas Pub Date : 2025-06-16 DOI:10.1186/s41065-025-00463-y

Huang Xiaolong, Deng Min, Zhang Sizhou, Hu Daorong, Pan Juncheng, Wang Yanjian, Li Jie Gu Hong, Zheng Ji, Wu Qingjian

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引用次数: 0

Abstract

Background: Previous studies have demonstrated a close association between neddylation modifications and tumor progression as well as alterations in the microenvironment. This study aimed to explore the role of neddylation in bladder cancer (BLCA) progression and its prognostic significance.

Methods: Gene expression data from the TCGA database were analyzed to identify neddylation gene modules using the limma software package and weighted gene co-expression network analysis (WGCNA). Prognostic models based on neddylation-related genes were subsequently developed through LASSO and Cox regression analyses. Additionally, a protein-protein interaction (PPI) network, gene set enrichment analysis (GSEA), and BLCA single-cell sequencing data were utilized to explore the functional roles of hub genes in BLCA and their impact on biological pathways. The expression of these hub genes was further validated in clinical samples via RT-qPCR.

Results: WGCNA analysis revealed 1412 neddylation-related hub genes. LASSO and Cox regression analyses subsequently identified six key genes: CUL1, PUM2, UBE2D3, HIF3A, COPS2, and DDB1. Transcriptomic data and RT-qPCR findings indicated that PUM2 and HIF3A exhibited high expression levels in normal tissues, while DDB1 showed increased expression in tumor tissues; no significant changes were observed for CUL1, COPS2, and UBE2D3. By integrating these gene expressions with significant clinical features, a prognostic model was constructed that demonstrated excellent diagnostic efficiency (AUC: 0.793 at 1 year, 0.792 at 3 years, and 0.773 at 5 years). In addition, single cell sequencing highlighted the potential role of these genes in modulating immune responses and mediating interactions between tumor cells and immune cells. GSEA also suggested that DDB1 may play a crucial role in orchestrating key biological processes associated with BLCA, particularly in activating apoptotic signaling pathways.

Conclusion: The six neddylation-related genes (CUL1, PUM2, UBE2D3, HIF3A, COPS2, and DDB1) emerge as potential independent indicators of survival in patients with BLCA, and the constructed survival models exhibit significant diagnostic efficacy.

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与泛素化相关基因的膀胱癌预后分析。

背景：先前的研究已经证明类化修饰与肿瘤进展以及微环境的改变密切相关。本研究旨在探讨类化修饰在膀胱癌（BLCA）进展中的作用及其预后意义。方法：利用limma软件包和加权基因共表达网络分析法（WGCNA）对TCGA数据库中的基因表达数据进行分析，鉴定类化修饰基因模块。随后通过LASSO和Cox回归分析建立了基于类化化相关基因的预后模型。此外，利用蛋白-蛋白相互作用（PPI）网络、基因集富集分析（GSEA）和BLCA单细胞测序数据，探讨了枢纽基因在BLCA中的功能作用及其对生物学途径的影响。通过RT-qPCR在临床样本中进一步验证了这些枢纽基因的表达。结果：WGCNA分析共发现1412个类泛素化相关枢纽基因。LASSO和Cox回归分析随后确定了6个关键基因：CUL1、PUM2、UBE2D3、HIF3A、COPS2和DDB1。转录组学数据和RT-qPCR结果显示，PUM2和HIF3A在正常组织中高表达，DDB1在肿瘤组织中高表达；CUL1、COPS2和UBE2D3未见明显变化。通过将这些基因表达与重要的临床特征整合，构建了一个预后模型，该模型具有出色的诊断效率（AUC: 1年0.793,3年0.792,5年0.773）。此外，单细胞测序强调了这些基因在调节免疫反应和介导肿瘤细胞与免疫细胞之间相互作用中的潜在作用。GSEA还表明，DDB1可能在协调与BLCA相关的关键生物学过程中发挥关键作用，特别是在激活凋亡信号通路方面。结论：6个类木化修饰相关基因CUL1、PUM2、UBE2D3、HIF3A、COPS2、DDB1成为BLCA患者潜在的独立生存指标，构建的生存模型具有显著的诊断效果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hereditas Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.80

自引率

3.70%

发文量

期刊介绍： For almost a century, Hereditas has published original cutting-edge research and reviews. As the Official journal of the Mendelian Society of Lund, the journal welcomes research from across all areas of genetics and genomics. Topics of interest include human and medical genetics, animal and plant genetics, microbial genetics, agriculture and bioinformatics.