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A Novel Proteomics Approach to Identify Serum and Urinary Biomarkers and Pathways that Associate with Lower Urinary Tract Symptoms in Men and Women: Pilot Results of the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) Study.

ABSTRACT: OBJECTIVES: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. METHODS: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. RESULTS: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. CONCLUSION: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.

SUBMITTER: Helfand BT

PROVIDER: S-EPMC6592754 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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A Novel Proteomics Approach to Identify Serum and Urinary Biomarkers and Pathways that Associate with Lower Urinary Tract Symptoms in Men and Women: Pilot Results of the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) Study.

Helfand Brian T BT Andreev Victor P VP Siddiqui Nazema Y NY Liu Gang G Erickson Bradley A BA Helmuth Margaret E ME Lutgendorf Susan K SK Lai H Henry HH Kirkali Ziya Z

Urology 20190325

<h4>Objectives</h4>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.<h4>Methods</h4>Eighteen male and 18 female symptoms of lower urinary tract dysfunction ...[more]

PMID: 30922973

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Project description:BackgroundIn men aged above 50 yr, lower urinary tract symptoms (LUTS), benign prostate hyperplasia, and prostate cancer are common urological conditions. Current guidelines for general practitioners frequently recommend prostate-specific antigen (PSA) testing in patients with LUTS for the detection of prostate cancer.ObjectiveTo assess the performance of PSA, PSA density, and the Stockholm3 blood test for identification of prostate cancer among men with LUTS.Design setting and participantsIn this post hoc analysis of a population-based diagnostic trial (STHLM3, n = 58 588), 4588 men aged 50-69 yr, without previous prostate cancer, with International Prostate Symptom Score (IPSS) data, and having PSA ≥ 3 ng/mL were identified. Men with at least moderate LUTS, defined as an IPSS score of ≥8, were included. PSA density and Stockholm3 scores were calculated.InterventionParticipants underwent 10-12-core systematic prostate biopsies.Outcome measurements and statistical analysisThe primary outcome was significant prostate cancer (sPCa) defined as International Society of Urological Pathology (ISUP) grade ≥2. Logistic regression analysis adjusted for age and previous biopsy status was performed. The area under the receiver operating characteristic curve (AUC) was calculated, and decision curve analysis was performed.Results and limitationsOut of 4588 men, 1544 (34%) reported at least moderate LUTS. The median age was 64 yr, and 11% had undergone a previous prostate biopsy. The Stockholm3 test showed superior discrimination for sPCa to PSA density, which in turn showed superior discrimination to PSA (AUC 0.77 vs 0.70 vs 0.61, p < 0.02). Calibration of the Stockholm3 test was adequate. Performing biopsy only in men with PSA ≥5 ng/mL saved 64% of biopsies, but resulted in missing 52% of detectable sPCa. Recommending biopsy for men with PSA density ≥0.07 resulted in sparing 26% of biopsy procedures and delaying the diagnosis of 12% of sPCa cases, with a 6.1% risk of sPCa among unbiopsied men. Recommending men with Stockholm3 ≥ 0.11 for biopsy resulted in sparing 53% of biopsy procedures and delaying the diagnosis of 20% of sPCa cases, with a 5.1% risk of finding sPCa in unbiopsied men.ConclusionsPSA density and the Stockholm3 blood test were superior to PSA for the identification of prostate cancer among men with LUTS.Patient summaryIn this analysis of a large Swedish study, we find that the use of prostate-specific antigen (PSA) density or the Stockholm3 blood test instead of only PSA might improve the detection of prostate cancer among men with lower urinary tract symptoms.

Project description:INTRODUCTION:Dipstick urinalysis is a widely used screening tool in the evaluation of men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). As limited data support the use of dipstick urinalysis, we have used data from three recently published studies to assess clinical outcomes in those who had dipstick urinalysis findings for blood, glucose, and/or leukocytes. METHODS:We analyzed data from three observational studies involving men interested in using over-the-counter tamsulosin: a self-selection study (SSS) and two actual-use studies of 8-week (AUS8) and 24-week (AUS24) durations. Subgroup analyses focused on pooled data from participants not using α-blockers or other prescription medication for LUTS suggestive of BPH (nonRx users) and who had urine dipstick findings. Data from participants using α-blockers (AUS8) or any prescription BPH medications (SSS and AUS24) are presented as reference. RESULTS:Overall, 2488 nonRx users underwent dipstick urinalysis and 680 (27.3%) had positive findings including traces of blood (332; 13.3%), glucose (259; 10.4%), and/or leukocytes (245; 9.8%). Among users of prescription medicines, 21.6% (37/171) in SSS, 27.4% (23/84) in AUS8, and 31.1% (47/151) in AUS24 had urine dipstick findings. The 200 dipstick-positive nonRx users in SSS underwent per protocol urological assessment: 26 (13.0%) had a newly diagnosed condition causing/contributing to urinary symptoms of which 2.9% were identified as medically important conditions. Among nonRx users with or without a dipstick finding, medically important conditions reported included prostate cancer (1.0% vs. 1.0%, respectively) and urolithiasis (1.0% vs. 0.3%, respectively). The proportion of men with dipstick urinalysis findings was similar between men who regularly visited their physician and those who did not. CONCLUSION:Dipstick urinalysis did not markedly increase the detection of undiagnosed medically important conditions that cause/contribute to urinary symptoms, suggesting that this test may not be a very effective screening tool for men with LUTS. FUNDING:Boehringer Ingelheim Pharmaceuticals, Inc.

Dataset Information

A Novel Proteomics Approach to Identify Serum and Urinary Biomarkers and Pathways that Associate with Lower Urinary Tract Symptoms in Men and Women: Pilot Results of the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) Study.

Publications

A Novel Proteomics Approach to Identify Serum and Urinary Biomarkers and Pathways that Associate with Lower Urinary Tract Symptoms in Men and Women: Pilot Results of the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) Study.

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