Department of Urology, Fujian Medical University Affiliated Quanzhou First Hospital, Fujian, 362011, China.
Zhangjiang Center for Translational Medicine, Shanghai Biotecan Biotechnology Co., Ltd., 180 Zhangheng Road, Pudong District, Shanghai, 201204, China.
J Transl Med. 2024 Jul 5;22(1):628. doi: 10.1186/s12967-024-05446-7.
Bladder cancer is a common malignancy with high recurrence rate. Early diagnosis and recurrence surveillance are pivotal to patients' outcomes, which require novel minimal-invasive diagnostic tools. The urinary microbiome is associated with bladder cancer and can be used as biomarkers, but the underlying mechanism is to be fully illustrated and diagnostic performance to be improved.
A total of 23 treatment-naïve bladder cancer patients and 9 non-cancerous subjects were enrolled into the Before group and Control group. After surgery, 10 patients from the Before group were further assigned into After group. Void mid-stream urine samples were collected and sent for 16S rDNA sequencing, targeted metabolomic profiling, and flow cytometry. Next, correlations were analyzed between microbiota, metabolites, and cytokines. Finally, receiver operating characteristic (ROC) curves of the urinary biomarkers were plotted and compared.
Comparing to the Control group, levels of IL-6 (p < 0.01), IL-8 (p < 0.05), and IL-10 (p < 0.05) were remarkably elevated in the Before group. The α diversity of urine microbiome was also significantly higher, with the feature microbiota positively correlated to the level of IL-6 (r = 0.58, p < 0.01). Significant differences in metabolic composition were also observed between the Before and Control groups, with fatty acids and fatty acylcarnitines enriched in the Before group. After tumor resection, cytokine levels and the overall microbiome structure in the After group remained similar to that of the Before group, but fatty acylcarnitines were significantly reduced (p < 0.05). Pathway enrichment analysis revealed beta-oxidation of fatty acids was significantly involved (p < 0.001). ROC curves showed that the biomarker panel of Actinomycetaceae + arachidonic acid + IL-6 had superior diagnostic performance, with sensitivity of 0.94 and specificity of 1.00.
Microbiome dysbiosis, proinflammatory environment and altered fatty acids metabolism are involved in the pathogenesis of bladder cancer, which may throw light on novel noninvasive diagnostic tool development.
膀胱癌是一种常见的恶性肿瘤，具有较高的复发率。早期诊断和复发监测对患者的预后至关重要，这需要新的微创诊断工具。尿液微生物组与膀胱癌相关，可以作为生物标志物，但潜在的机制尚需充分阐明，诊断性能也需要提高。
共纳入 23 例初治膀胱癌患者和 9 例非癌患者进入术前组和对照组。术后，术前组 10 例患者进一步分为术后组。收集中段尿液样本进行 16S rDNA 测序、靶向代谢组学分析和流式细胞术分析。然后分析微生物群、代谢物和细胞因子之间的相关性。最后绘制并比较尿液生物标志物的受试者工作特征（ROC）曲线。
与对照组相比，术前组白细胞介素 6（IL-6）（p<0.01）、白细胞介素 8（IL-8）（p<0.05）和白细胞介素 10（IL-10）（p<0.05）水平显著升高。尿液微生物组的 α 多样性也显著增加，特征微生物群与 IL-6 水平呈正相关（r=0.58，p<0.01）。术前组和对照组之间的代谢物组成也存在显著差异，脂肪酸和脂肪酸酰基辅酶 A 在术前组中富集。肿瘤切除后，术后组的细胞因子水平和整体微生物组结构与术前组相似，但脂肪酸酰基辅酶 A 显著减少（p<0.05）。途径富集分析显示，脂肪酸的β氧化明显参与其中（p<0.001）。ROC 曲线显示，放线菌科+花生四烯酸+IL-6 的生物标志物组合具有较好的诊断性能，敏感性为 0.94，特异性为 1.00。
微生物组失调、促炎环境和脂肪酸代谢改变与膀胱癌的发病机制有关，这可能为开发新的非侵入性诊断工具提供线索。
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