利用缺氧相关基因标记预测膀胱癌预后。

IF 1.7 3区 医学 Q4 ANDROLOGY
Translational andrology and urology Pub Date : 2025-06-30 Epub Date: 2025-06-26 DOI:10.21037/tau-2025-118
Yang Dong, Yu-Ang Chen, Pei-Ze Yu, Qiang Liu, Ran Zhou, Hui Yu, Zhen-Duo Shi, Lin Hao, Tong Zhao, Jun Ding, Cong-Hui Han
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引用次数: 0

摘要

背景:缺氧在实体肿瘤中很常见,促进肿瘤生长和治疗抵抗,对优化患者预后至关重要,但对膀胱癌(BC)缺氧机制的研究仍然有限。本研究旨在探讨缺氧相关基因(HRGs)在BC中的功能作用。方法:从GeneCards中获取hrg,通过单样本基因集富集分析(ssGSEA)评估BC患者的缺氧评分。使用差异表达的预后hrg构建预后风险模型,并通过随时间变化的受试者工作特征(ROC)曲线、Kaplan-Meier (KM)曲线和正态图分析进行评估。分析高危组和低危组的差异特征,包括临床特征、生物学功能、突变谱、免疫浸润和药物敏感性。我们利用实时定量聚合酶链反应(qRT-PCR)技术在体外检测hub基因的表达,评估其与特殊草药单体的相互作用,并利用BC的单细胞测序数据评估其发育轨迹。结果:基于ROC和KM分析,缺氧评分系统在BC诊断和预后预测方面是有效的。使用JUN、MYC、EGFR和SLC2A1构建预后风险模型,并对BC风险进行有效分层。许多突变,尤其是常见的TP53,都发生在两个风险组中。此外,高危组免疫细胞浸润较多。此外,预计茄碱和大黄碱对枢纽基因,特别是EGFR和SLC2A1具有良好的结合亲和力。此外,使用单细胞数据证实,恶性上皮细胞在BC中占主导地位,JUN在发育轨迹上有显著变化,MYC在发育终点增加,突出了它们在BC进展中的关键作用。结论:我们建立了一种新的预后风险模型,作为BC患者的独立预测因子,为BC的免疫微环境和致癌机制提供了新的见解。在这个模型中分析突变模式、药物敏感性和基因的发育轨迹将有助于改进治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Leveraging hypoxia-related genes signature for predicting the prognosis of bladder cancer.

Background: Hypoxia is common in solid tumors, facilitating tumor growth and treatment resistance, and is crucial for optimizing patient outcomes, but research on the mechanism of hypoxia in bladder cancer (BC) remains limited. This study aims to explore the functional role of hypoxia-related genes (HRGs) in BC.

Methods: The HRGs were obtained from GeneCards, and the hypoxia score in BC patients was evaluated by single-sample gene set enrichment analysis (ssGSEA). The prognostic risk model was constructed using differentially expressed prognostic HRGs, and assessed via time-dependent receiver operating characteristic (ROC) curves, Kaplan-Meier (KM) curve, and nomogram analysis. Differential features between high- and low-risk groups were analyzed, including clinical characteristics, biological functions, mutation profiles, immune infiltration, and drug sensitivity. We measured the expression of hub genes in vitro via quantitative real-time polymerase chain reaction (qRT-PCR), assessed their interactions with special herbal monomers, and evaluated the developmental trajectories using single-cell sequencing data of BC.

Results: The hypoxia score system was proven effective in BC diagnosis and prognostic prediction based on ROC and KM analyses. The prognostic risk model was constructed with JUN, MYC, EGFR, and SLC2A1, and effectively stratified BC risk. Numerous mutations, especially the frequent TP53, occurred in both risk groups. Besides, the high-risk group exhibited more immune cell infiltration. Moreover, solasonine and rhein were predicted to exhibit well binding affinity for hub genes, especially EGFR and SLC2A1. Additionally, a predominance of malignant epithelial cells in BC was confirmed using single-cell data, with significant variation in JUN along the developmental trajectory and an increase of MYC at developmental endpoint, highlighting their critical roles in BC progression.

Conclusions: We developed a novel prognostic risk model as an independent predictor for BC patients, which offers insights into immune microenvironment and carcinogenesis mechanisms of BC. Analyzing mutation patterns, drug sensitivities, and the developmental trajectories of genes within this model would be helpful for refining therapeutic strategies.

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来源期刊
CiteScore
4.10
自引率
5.00%
发文量
80
期刊介绍: ranslational Andrology and Urology (Print ISSN 2223-4683; Online ISSN 2223-4691; Transl Androl Urol; TAU) is an open access, peer-reviewed, bi-monthly journal (quarterly published from Mar.2012 - Dec. 2014). The main focus of the journal is to describe new findings in the field of translational research of Andrology and Urology, provides current and practical information on basic research and clinical investigations of Andrology and Urology. Specific areas of interest include, but not limited to, molecular study, pathology, biology and technical advances related to andrology and urology. Topics cover range from evaluation, prevention, diagnosis, therapy, prognosis, rehabilitation and future challenges to urology and andrology. Contributions pertinent to urology and andrology are also included from related fields such as public health, basic sciences, education, sociology, and nursing.
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