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膀胱癌衰老相关基因风险评分模型及其在临床预后中的应用

Risk Score Model of Aging-Related Genes for Bladder Cancer and Its Application in Clinical Prognosis.

作者信息

Lu Kun, Chao Liu, Wang Jin, Wang Xiangyu, Cai Longjun, Zhang Jianjun, Zhang Shaoqi

机构信息

Department of Oncology, The Specialized Suqian Hospital of Xuzhou Medical University, Suqian, China.

Department of Oncology, Suqian Hospital of Nanjing Drum Tower Hospital Group, Suqian, China.

出版信息

JCO Clin Cancer Inform. 2025 Aug;9:e2500019. doi: 10.1200/CCI-25-00019. Epub 2025 Aug 8.


DOI:10.1200/CCI-25-00019
PMID:40779729
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12360192/
Abstract

PURPOSE: Bladder cancer (BLCA) ranks as the tenth most common malignancy worldwide, with rising incidence and mortality rates. Owing to its molecular and clinical heterogeneity, BLCA is associated with high rates of recurrence and metastasis after surgery, contributing to a poor 5-year survival rate. There is a pressing need for highly sensitive and specific molecular biomarkers to enable early identification of high-risk patients, guide clinical management, and improve patient outcomes. This study aimed to develop a prognostic model on the basis of aging-related genes (ARGs) to evaluate survival outcomes and immunotherapy responsiveness in patients with BLCA, and to further explore its relevance to the tumor immune microenvironment and drug sensitivity. MATERIALS AND METHODS: Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus were used to construct a 12-gene ARG-based prognostic signature through LASSO and Cox regression analyses. Patients were stratified into high-risk and low-risk groups according to the median risk score. Kaplan-Meier survival curves, receiver operating characteristic analyses, and nomograms were used to assess the predictive value of the model. Univariate and multivariate Cox regression analyses were conducted to determine its prognostic independence. RESULTS: Twelve ARGs were identified. Patients in the low-risk group exhibited significantly better overall survival ( < .0001). In the TCGA cohort, the model yielded AUC values ranging from 0.772 to 0.794 across 1-5 years. Cox regression confirmed the ARG score as an independent prognostic indicator. External validation using the GSE32894 data set supported its clinical reliability. The ARG signature was also associated with immune cell infiltration and predicted chemosensitivity. CONCLUSION: The ARG-based risk score independently predicts clinical prognosis in BLCA and correlates with immune microenvironment characteristics, offering potential value in guiding personalized treatment strategies.

摘要

目的:膀胱癌(BLCA)是全球第十大常见恶性肿瘤,其发病率和死亡率呈上升趋势。由于其分子和临床异质性,BLCA患者术后复发和转移率较高,导致5年生存率较低。迫切需要高度敏感和特异的分子生物标志物,以早期识别高危患者,指导临床管理并改善患者预后。本研究旨在基于衰老相关基因(ARG)建立一个预后模型,以评估BLCA患者的生存结果和免疫治疗反应性,并进一步探讨其与肿瘤免疫微环境和药物敏感性的相关性。 材料与方法:使用来自癌症基因组图谱(TCGA)和基因表达综合数据库的转录组学和临床数据,通过LASSO和Cox回归分析构建基于12个基因的ARG预后特征。根据中位风险评分将患者分为高风险和低风险组。采用Kaplan-Meier生存曲线、受试者工作特征分析和列线图评估模型的预测价值。进行单因素和多因素Cox回归分析以确定其预后独立性。 结果:鉴定出12个ARG。低风险组患者的总生存期显著更好(<0.0001)。在TCGA队列中,该模型在1至5年期间的AUC值范围为0.772至0.794。Cox回归证实ARG评分是一个独立的预后指标。使用GSE32894数据集进行的外部验证支持了其临床可靠性。ARG特征还与免疫细胞浸润相关并预测化疗敏感性。 结论:基于ARG的风险评分可独立预测BLCA的临床预后,并与免疫微环境特征相关,在指导个性化治疗策略方面具有潜在价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4152/12360192/10f87a161a09/cci-9-e2500019-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4152/12360192/363789420912/cci-9-e2500019-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4152/12360192/75627888ae56/cci-9-e2500019-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4152/12360192/3a070d995054/cci-9-e2500019-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4152/12360192/f46c3b8853a5/cci-9-e2500019-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4152/12360192/363789420912/cci-9-e2500019-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4152/12360192/10f87a161a09/cci-9-e2500019-g007.jpg

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本文引用的文献

[1]
Advancing bladder cancer management: development of a prognostic model and personalized therapy.

Front Immunol. 2024

[2]
Single-cell and bulk RNA-sequence identified fibroblasts signature and CD8 + T-cell - fibroblast subtype predicting prognosis and immune therapeutic response of bladder cancer, based on machine learning: bioinformatics multi-omics study.

Int J Surg. 2024-8-1

[3]
CD276-dependent efferocytosis by tumor-associated macrophages promotes immune evasion in bladder cancer.

Nat Commun. 2024-4-1

[4]
Comprehensive analysis of PRPF19 immune infiltrates, DNA methylation, senescence-associated secretory phenotype and ceRNA network in bladder cancer.

Front Immunol. 2023

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The Impact of FGFR3 Alterations on the Tumor Microenvironment and the Efficacy of Immune Checkpoint Inhibitors in Bladder Cancer.

Mol Cancer. 2023-11-18

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Senescent alveolar macrophages promote early-stage lung tumorigenesis.

Cancer Cell. 2023-7-10

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[8]
ETV4 Mediated Tumor-Associated Neutrophil Infiltration Facilitates Lymphangiogenesis and Lymphatic Metastasis of Bladder Cancer.

Adv Sci (Weinh). 2023-4

[9]
Advances in Immunotherapy and the TGF-β Resistance Pathway in Metastatic Bladder Cancer.

Cancers (Basel). 2021-11-16

[10]
Cellular aging beyond cellular senescence: Markers of senescence prior to cell cycle arrest in vitro and in vivo.

Aging Cell. 2021-4

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