Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of urothelial carcinoma (UC); however, their efficacy varies among patients. Identifying reliable biomarkers to predict response to ICIs remains challenging. We aimed to explore urinary microRNAs (miRNAs) as potential biomarkers for predicting ICI efficacy in patients with UC.Methods: We prospectively collected urinary samples from patients with UC before ICI initiation and investigated the predictive value of urinary miRNAs in patients with UC receiving ICIs. The expression levels of these miRNAs in pretreated urine samples were analyzed using next-generation sequencing. The patients were categorized as responders (those with stable disease or better for >6 months) or nonresponders (those who experienced disease progression within 6 months of treatment initiation). Urinary miRNA levels were compared between the groups to assess their potential as predictive biomarkers.Results: Elevated expression of miR-185-5p and miR-425-5p in the responder group was significantly associated with improved overall and progression-free survival in patients with bladder cancer treated with ICIs (p< 0.05). Conversely, higher levels of miR-30a-5p and miR-542-3p in the nonresponder group were correlated with a poorer response to ICIs, suggesting a potential role in immune resistance.Conclusions: miR-185-5p and miR-425-5p can serve as predictive biomarkers of favorable ICI efficacy in bladder cancer, whereas miR-30a-5p and miR-542-3p could be associated with resistance mechanisms. These findings highlight the potential of miRNA-based biomarkers, particularly those found in urine samples, to guide personalized immunotherapeutic strategies for UC treatment.
背景：免疫检查点抑制剂（ICIs）已彻底改变了尿路上皮癌（UC）的治疗格局，但其疗效在患者间存在差异。寻找可靠的生物标志物来预测患者对ICIs的反应仍具挑战。本研究旨在探索尿液微小核糖核酸（miRNAs）作为预测UC患者ICI疗效的潜在生物标志物。 方法：我们前瞻性地收集了UC患者在开始ICI治疗前的尿液样本，并研究了尿液miRNAs对接受ICI治疗的UC患者的预测价值。通过新一代测序技术分析了治疗前尿液样本中这些miRNAs的表达水平。患者被分为应答组（疾病稳定或更好状态持续超过6个月）和无应答组（治疗开始后6个月内出现疾病进展）。通过比较两组间尿液miRNA水平，评估其作为预测性生物标志物的潜力。 结果：在应答组中，miR-185-5p和miR-425-5p的表达升高与接受ICI治疗的膀胱癌患者的总生存期和无进展生存期改善显著相关（p<0.05）。相反，无应答组中较高水平的miR-30a-5p和miR-542-3p与较差的ICI反应相关，提示这些miRNAs可能在免疫抵抗机制中发挥作用。 结论：miR-185-5p和miR-425-5p可作为膀胱癌患者ICI疗效良好的预测性生物标志物，而miR-30a-5p和miR-542-3p可能与耐药机制相关。这些发现凸显了基于miRNA的生物标志物（特别是在尿液样本中检测到的标志物）在指导UC个体化免疫治疗策略方面的潜力。
肿瘤(癌症)患者之家