与双酚 A 促成的膀胱癌相关成纤维细胞 (CAF) 有关的新治疗靶点和生物标记物

IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Yuan Luo, Xinyue Liu, Yuanting Liu
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引用次数: 0

摘要

与环境污染物,特别是干扰内分泌的化学品(EDCs)有关的健康问题日益增多,已成为现代工业化的一个严重后果。双酚 A(BPA)是一种广泛存在的 EDC,由于其通过调节癌症相关成纤维细胞(CAFs)而加剧膀胱癌的潜在作用而受到关注。CAFs 是肿瘤微环境不可或缺的组成部分,通过与免疫细胞的相互作用以及分泌各种因子和外泌体影响癌症的进展。认识到CAFs的关键作用,本研究深入研究了它们作为治疗靶点的效用,重点是鉴定CAFs中治疗膀胱癌的可靠生物标志物。通过加权相关网络分析,确定了与 T 细胞活性相关的基因,最终建立了基于 CAFs 的免疫相关基因预后模型。ANPEP是该模型的核心基因,这种酶的表达水平不仅是T细胞浸润的指标,而且在CAF介导的膀胱癌免疫治疗反应中发挥着重要作用。我们的研究认为,ANPEP 是调节 CAF 功能的关键因素,这提供了一个新的视角,即靶向 ANPEP 可减少传统免疫疗法常见的不良副作用。此外,ANPEP靶向策略还能减轻膀胱癌患者的肿瘤突变负担。我们的增殖和侵袭试验提供的经验证据表明,ANPEP的高表达与患者生存率的降低有关。这些见解为膀胱癌治疗中的定制免疫疗法铺平了道路,强调了 ANPEP 对 CAFs 的调节作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Novel Therapeutic Targets and Biomarkers Associated with Bladder Cancer-Associated Fibroblasts (CAFs) Promoted by Bisphenol A

Novel Therapeutic Targets and Biomarkers Associated with Bladder Cancer-Associated Fibroblasts (CAFs) Promoted by Bisphenol A

The escalating incidence of health issues linked to environmental pollutants, specifically endocrine-disrupting chemicals (EDCs), has emerged as a dire consequence of modern industrialization. Bisphenol A (BPA), a widespread EDC, is under scrutiny for its potential role in exacerbating bladder cancer via the modulation of cancer-associated fibroblasts (CAFs). CAFs are integral to the tumor microenvironment, influencing cancer progression through their interactions with immune cells and secretion of various factors and exosomes. By recognizing the critical role of CAFs, this study delves into their utility as therapeutic targets, focusing on the identification of reliable biomarkers within CAFs for bladder cancer. Through weighted correlation network analysis, genes associated with T cell activity were pinpointed, culminating in the creation of a CAFs-based, immune-related gene prognostic model. Central to this model is ANPEP, an enzyme whose expression level not only serves as an indicator of T cell infiltration but also implicates a substantial role in the CAF-mediated immunotherapy responses for bladder cancer. Our investigation posits ANPEP as a linchpin in regulating CAF functions, offering a novel perspective wherein targeting ANPEP may reduce the adverse side effects commonly associated with traditional immunotherapies. Furthermore, ANPEP-targeted strategies could lessen the tumor mutational burden in bladder cancer patients. Empirical evidence from our proliferation and invasion assays indicates that heightened ANPEP expression is correlated with diminished patient survival. These insights pave the way for tailored immunotherapeutic approaches in bladder cancer treatment, emphasizing the modulation of CAFs by ANPEP.

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来源期刊
CiteScore
4.10
自引率
5.00%
发文量
226
审稿时长
6 months
期刊介绍: The Journal of Clinical Pharmacy and Therapeutics provides a forum for clinicians, pharmacists and pharmacologists to explore and report on issues of common interest. Reports and commentaries on current issues in medical and pharmaceutical practice are encouraged. Papers on evidence-based clinical practice and multidisciplinary collaborative work are particularly welcome. Regular sections in the journal include: editorials, commentaries, reviews (including systematic overviews and meta-analyses), original research and reports, and book reviews. Its scope embraces all aspects of clinical drug development and therapeutics, including: Rational therapeutics Evidence-based practice Safety, cost-effectiveness and clinical efficacy of drugs Drug interactions Clinical impact of drug formulations Pharmacogenetics Personalised, stratified and translational medicine Clinical pharmacokinetics.
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