NorthShore University Health System, Evanston IL.
Arbor Research Collaborative for Health, Ann Arbor MI.
Urology. 2019 Jul;129:35-42. doi: 10.1016/j.urology.2019.03.014. Epub 2019 Mar 25.
To assess the feasibility of a novel proteomics approach to identify biomarkers associated with lower urinary tract symptoms (LUTS) within serum and urine, because many clinical factors contribute to LUTS in men and women. These factors confound clinicians' abilities to reliably evaluate and treat LUTS. Previous studies identified candidate LUTS biomarkers, but none are clinically utilized.
Eighteen male and 18 female symptoms of lower urinary tract dysfunction research network (LURN) observational cohort study participants with LUTS (measured on the LUTS Tool questionnaire) were randomly selected. Twelve male and 12 female controls with minimal or no LUTS were recruited and matched for clinico-demographic characteristics. The SomaScan Assay (SomaLogic) was used to measure the abundance of 1305 proteins contained within urine and serum. Statistical analyses were performed to evaluate reproducibility of assays, compare protein abundances, and estimate effect size.
SomaScan assay results were more reproducible in serum than in urine. Within serum, there were many more differentially abundant proteins between cases and controls in males than in females. An enrichment/pathway analysis of the affected proteins in male and female subjects demonstrated that the enriched Gene Ontology processes were related to prostate morphogenesis in men and growth and inflammation in women.
The pilot study results support that the etiology and pathophysiologic mechanisms underlying LUTS may be sex-specific. While further studies involving larger numbers of subjects are warranted, our results support the feasibility of a novel proteomic approach to identify biomarkers for diagnostic classification of LUTS.
评估一种新的蛋白质组学方法鉴定与下尿路症状(LUTS)相关生物标志物的可行性,因为许多临床因素会导致男性和女性的 LUTS。这些因素干扰了临床医生可靠评估和治疗 LUTS 的能力。先前的研究确定了候选 LUTS 生物标志物,但没有一种在临床上得到应用。
随机选择 18 名男性和 18 名女性下尿路功能障碍研究网络(LURN)观察队列研究参与者,这些参与者有 LUTS(通过 LUTS 工具问卷测量)。招募了 12 名男性和 12 名女性对照组,他们的 LUTS 症状很少或没有,且临床人口统计学特征相匹配。使用 SomaScan 分析(SomaLogic)测量尿液和血清中包含的 1305 种蛋白质的丰度。进行统计分析以评估分析的可重复性、比较蛋白质丰度和估计效应量。
与尿液相比,SomaScan 分析在血清中的结果更具可重复性。在血清中,男性病例和对照组之间差异表达的蛋白质比女性更多。对男性和女性受影响蛋白质的富集/途径分析表明,受影响的基因本体过程与男性前列腺形态发生以及女性生长和炎症有关。
初步研究结果支持 LUTS 的病因和病理生理机制可能具有性别特异性。虽然需要进一步涉及更多受试者的研究,但我们的结果支持使用新的蛋白质组学方法来鉴定 LUTS 诊断分类的生物标志物的可行性。