Cedars-Sinai Medical Center, Los Angeles, CA.
Veterans Affairs Health Care System, Durham, NC.
Urology. 2021 Nov;157:85-92. doi: 10.1016/j.urology.2021.05.005. Epub 2021 May 17.
To identify the potential biomarkers of interstitial cystitis/painful bladder syndrome (IC), a chronic syndrome of bladder-centric pain with unknown etiology that has an adverse impact on quality of life, we analyzed the urine and serum metabolomes of a cohort of IC patients and non-disease controls (NC).
Home collection of serum and urine samples was obtained from 19 IC and 20 NC females in the Veterans Affairs (VA) Health Care System. IC was diagnosed independently by thorough review of medical records using established criteria. Biostatistics and bioinformatics analyses, including univariate analysis, unsupervised clustering, random forest analysis, and metabolite set enrichment analysis (MSEA), were then utilized to identify potential IC biomarkers.
Metabolomics profiling revealed distinct expression patterns between NC and IC. Random forest analysis of urine samples suggested discriminators specific to IC; these include phenylalanine, purine, 5-oxoproline, and 5-hydroxyindoleacetic acid. When these urinary metabolomics-based analytes were combined into a single model, the AUC was 0.92, suggesting strong potential clinical value as a diagnostic signature. Serum-based metabolomics did not provide potential IC discriminators.
Analysis of serum and urine revealed that women with IC have distinct metabolomes, highlighting key metabolic pathways that may provide insight into the pathophysiology of IC. The findings from this pilot study suggest that integrated analyses of urinary metabolites, purine, phenylalanine, 5-oxoproline, and 5-HIAA, can lead to promising IC biomarkers for pathophysiology of IC. Validation of these results using a larger dataset is currently underway.
为了鉴定间质性膀胱炎/膀胱疼痛综合征(IC)的潜在生物标志物。IC 是一种以膀胱为中心的慢性疼痛综合征,病因不明,对生活质量有不良影响。我们分析了一组 IC 患者和非疾病对照(NC)的尿液和血清代谢组。
在退伍军人事务部(VA)医疗保健系统中,收集了 19 名 IC 和 20 名 NC 女性的血清和尿液样本。IC 是通过使用既定标准对病历进行彻底审查独立诊断的。然后利用生物统计学和生物信息学分析,包括单变量分析、无监督聚类、随机森林分析和代谢物集富集分析(MSEA),来鉴定潜在的 IC 生物标志物。
代谢组学分析显示 NC 和 IC 之间存在明显的表达模式差异。尿液样本的随机森林分析表明,IC 具有特异性的鉴别物,包括苯丙氨酸、嘌呤、5-氧脯氨酸和 5-羟吲哚乙酸。当将这些基于尿液代谢组学的分析物组合成一个单一的模型时,AUC 为 0.92,表明其作为诊断特征具有很强的潜在临床价值。基于血清的代谢组学没有提供潜在的 IC 鉴别物。
对血清和尿液的分析表明,IC 女性的代谢组存在明显差异,突出了可能为 IC 病理生理学提供深入了解的关键代谢途径。这项初步研究的结果表明,综合分析尿液代谢物、嘌呤、苯丙氨酸、5-氧脯氨酸和 5-HIAA 可能为 IC 的病理生理学提供有前景的生物标志物。目前正在使用更大的数据集验证这些结果。