There are a total of 82,290 new cases and 16,710 deaths estimated for bladder cancer in the United States in 2023. Currently, urine cytology tests are widely used for bladder cancer diagnosis, though they suffer from variable sensitivity, ranging from 45 to 97%. More recently, the microbiome has become increasingly recognized for its role in human diseases, including cancers. This study attempts to characterize urinary microbiome bladder cancer-specific dysbiosis to explore its diagnostic potential. RNA-sequencing data of urine samples from patients with bladder cancer (n= 18) and matched controls (n= 12) were mapped to bacterial sequences to yield species-level abundance approximations. Urine samples were analyzed at both the population and species level to reveal dysbiosis associated with bladder cancer. A panel of 35 differentially abundant species was discovered, which may be useful as urinary biomarkers for this disease. We further assessed whether these species were of similar significance in a validation dataset (n= 81), revealing that the generaEscherichia,Acinetobacter, andEnterobacterwere consistently differentially abundant. We discovered distinct patterns of microbial-associated immune modulation in these samples. Several immune pathways were found to be significantly enriched with respect to the abundance of these species, including antigen processing and presentation, cytosolic DNA sensing, and leukocyte transendothelial migration. Differential cytokine activity was similarly observed, suggesting the urinary microbiome’s correlation to immune modulation. The adherens junction and WNT signaling pathways, both implicated in the development and progression of bladder cancer, were also enriched with these species. Our findings indicate that the urinary microbiome may reflect both microbial and immune dysregulations of the tumor microenvironment in bladder cancer. Given the potential biomarker species identified, the urinary microbiome may provide a non-invasive, more sensitive, and more specific diagnostic tool, allowing for the earlier diagnosis of patients with bladder cancer.
据估计，2023年美国膀胱癌新发病例总数达82,290例，死亡病例16,710例。目前尿液细胞学检测虽广泛应用于膀胱癌诊断，但其敏感性存在较大波动（45%-97%）。近年来微生物组在包括癌症在内的人类疾病中的作用日益受到重视。本研究旨在解析膀胱癌特异性尿液微生物组失调特征，探索其诊断潜力。通过将膀胱癌患者（n=18）与匹配对照组（n=12）尿液样本的RNA测序数据比对至细菌序列，获得物种水平丰度近似值。在群体和物种层面分析尿液样本，揭示与膀胱癌相关的菌群失调特征。研究鉴定出35种差异丰度物种，可作为该疾病的潜在尿液生物标志物。在验证数据集（n=81）中进一步评估这些物种的稳定性，发现埃希氏菌属、不动杆菌属和肠杆菌属持续呈现差异丰度特征。样本中观察到微生物相关免疫调节的特异性模式：抗原加工呈递、胞质DNA感知和白细胞跨内皮迁移等多条免疫通路与这些物种丰度显著相关；细胞因子活性差异同样表明尿液微生物组与免疫调节存在关联。与膀胱癌发生发展密切相关的粘附连接通路和WNT信号通路亦富集于这些物种。研究结果表明，尿液微生物组可能同时反映膀胱癌肿瘤微环境的微生物失调与免疫紊乱。基于已鉴定的潜在生物标志物物种，尿液微生物组有望提供一种非侵入性、更高敏感性及特异性的诊断工具，为膀胱癌患者实现更早期诊断。
肿瘤(癌症)患者之家