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

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.

本研究旨在通过构建基于髓系细胞分化相关基因（MCDGs）的预测基因特征，识别膀胱癌（BC）中的预后及治疗反应生物标志物，以优化患者管理。对来自TCGA和GEO数据库的BC患者数据采用非负矩阵分解（NMF）进行亚组分类，评估生存差异及通路变化。通过单变量Cox回归和LASSO分析构建预后MCDG模型，并利用Kaplan–Meier生存曲线和ROC曲线验证。此外，还评估了该模型的临床相关性、肿瘤微环境（TME）、药物反应及免疫治疗潜力。通过实时荧光定量聚合酶链式反应（qRT-PCR）及功能实验（包括Transwell迁移、划痕愈合、集落形成和EDU实验）验证了ACTN1的功能。NMF分析识别出两个BC亚组（CA和CB），其中CB亚组患者生存状况更佳。研究鉴定出6个与预后相关的关键MCDGs，高风险基因谱与较差预后相关。免疫浸润、检查点表达、TME及治疗反应方面存在显著差异。值得注意的是，沉默ACTN1可抑制BC细胞增殖。该MCDG特征可预测BC预后，并可能指导免疫治疗选择；ACTN1在BC增殖中起关键作用，凸显其作为治疗靶点的潜力。