Myeloid cell differentiation-related gene signature predicts the prognosis and immunotherapy response in bladder cancer.

IF 1.7 4区医学 Q3 COMPUTER SCIENCE, INTERDISCIPLINARY APPLICATIONS

Computer Methods in Biomechanics and Biomedical Engineering Pub Date : 2025-07-15 DOI:10.1080/10255842.2025.2532034

Lewei Guan, Fuchun Zheng, Sheng Li, Yuyang Yuan, Situ Xiong, Xiaoqiang Liu, Bin Fu

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Abstract

This study aims to identify prognostic and therapy-response biomarkers in bladder cancer (BC) by developing a predictive gene signature based on myeloid cell differentiation-related genes (MCDGs) to enhance patient management. BC patient data from TCGA and GEO were analyzed using non-negative matrix factorization (NMF) to classify subgroups. Survival differences and pathway variations were assessed. A prognostic MCDG model was constructed using univariate Cox regression and LASSO analyses, validated through Kaplan-Meier survival and ROC curves. Clinical relevance, tumor microenvironment (TME), drug response, and immunotherapy potential were evaluated. ACTN1 was verified via qRT-PCR and functional assays, including transwell migration, wound healing, colony formation, and EDU assays. NMF identified two BC subgroups (CA and CB), with CB showing better survival. Six key MCDGs linked to prognosis were identified. High-risk gene profiles correlated with poorer outcomes. Significant differences in immune infiltration, checkpoint expression, TME, and treatment response were observed. Notably, ACTN1 silencing suppressed BC cell proliferation. The MCDG signature predicts BC prognosis and may guide immunotherapy selection. ACTN1 is crucial in BC proliferation, highlighting its potential as a therapeutic target.

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骨髓细胞分化相关基因标记预测膀胱癌的预后和免疫治疗反应。

本研究旨在通过开发基于骨髓细胞分化相关基因（mcdg）的预测基因标记来识别膀胱癌（BC）的预后和治疗反应生物标志物，以加强患者管理。采用非负矩阵分解法（NMF）对TCGA和GEO的BC患者数据进行亚组分类。评估生存差异和途径变异。采用单变量Cox回归和LASSO分析构建预后MCDG模型，并通过Kaplan-Meier生存曲线和ROC曲线进行验证。评估临床相关性、肿瘤微环境（TME）、药物反应和免疫治疗潜力。ACTN1通过qRT-PCR和功能测定（包括跨井迁移、伤口愈合、菌落形成和EDU测定）进行验证。NMF鉴定出两个BC亚组（CA和CB），其中CB表现出更好的生存率。确定了与预后相关的6个关键mcdg。高风险基因与较差的结果相关。在免疫浸润、检查点表达、TME和治疗反应方面观察到显著差异。值得注意的是，ACTN1沉默抑制了BC细胞的增殖。MCDG标记可预测BC预后，并可指导免疫治疗的选择。ACTN1在BC增殖中起着至关重要的作用，突出了其作为治疗靶点的潜力。

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

Computer Methods in Biomechanics and Biomedical Engineering 工程技术-工程：生物医学

CiteScore

4.10

自引率

6.20%

发文量

179

审稿时长

4-8 weeks

期刊介绍： The primary aims of Computer Methods in Biomechanics and Biomedical Engineering are to provide a means of communicating the advances being made in the areas of biomechanics and biomedical engineering and to stimulate interest in the continually emerging computer based technologies which are being applied in these multidisciplinary subjects. Computer Methods in Biomechanics and Biomedical Engineering will also provide a focus for the importance of integrating the disciplines of engineering with medical technology and clinical expertise. Such integration will have a major impact on health care in the future.