Biomarkers Implicated in Lower Urinary Tract Symptoms: Systematic Review and Pathway Analyses

Abstract

Purpose: Lower urinary tract symptoms are prevalent and burdensome, yet methods to enhance diagnosis and appropriately guide therapies are lacking. We systematically reviewed the literature for human studies of biomarkers associated with lower urinary tract symptoms. Materials and Methods: PubMedÒ, EMBASEÒ and Web of ScienceÒ were searched from inception to February 13, 2018. Articles were included if they were in English, performed in benign urological populations without neurological disorders or interstitial cystitis/bladder pain syndrome, and assessed a biomarker's association with or ability to predict specific lower urinary tract symptoms or urological conditions. Bioinformatic pathway analyses were conducted to determine whether individual biomarkers associated with symptoms are present in unifying pathways. Results: Of 6,150 citations identified 125 met the inclusion criteria. Most studies (93.6%) assessed biomarkers at 1 time point and were crosssectional in nature. Few studies adjusted for potentially confounding clinical variables or assessed biomarkers in an individual over time. No individual biomarkers are currently validated as diagnostic tools for lower urinary tract symptoms. Compared to controls, pathway analyses identified multiple immune response pathways that were enriched in overactive bladder

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

“…Again, many studies have identified inflammatory pathways that contribute to female LUTS, including another pathway analysis specifically focused on overactive bladder where the majority of data came from female subjects. 13 While the proteins and pathways identified in this study implicate a role for inflammation and tissue growth in LUTS, they do not imply causation. If validated as biomarkers, future studies specifically evaluating their role in LUTS should be performed.…”

“…However, many of these are cross-sectional association studies and demonstrate conflicting results. 13 Similarly, proteomic studies conducted in humans and animals with bladder outlet obstruction have identified several candidate proteins that may be differentially expressed, including optineurin, thioredoxin, preprohaptoglobin, and Kallikrein-Related Peptidase 2 (KLK2). 20 However, the results of these studies have not been reproduced and, therefore, require further validation; future studies that use panels of biomarkers and can be rigorously validated will be extremely important.…”

“…[5][6][7] The multitude of processes that contribute to LUTS have confounded clinicians' abilities to reliably evaluate and quantify their presence. While previous studies have identified candidate biomarkers designed to accomplish this purpose, [8][9][10][11][12][13] no individual biomarker exists for diagnostic, prognostic, or predictive use in the clinical setting. This is likely related to the fact that most biomarker candidates were identified using a targeted approach evaluating only a limited panel of proteins, few have routinely been validated, and the associations between the biomarkers were only applicable to a subset of patients with specific LUTS (e.g., overactive bladder symptoms).…”

New participant stratification and combination of urinary biomarkers and confounders could improve diagnostic accuracy for overactive bladder

“…By measuring the urinary levels of IL-5 and ATP and entering their creatinine-normalised values, in addition to age and gender, in to the formula, the possibility of an individual being in the identified high OAB symptomatic score group could be predicted. This study provides the foundation for the development of novel non-invasive diagnostic tools for OAB, where the effects of biomarkers and key OAB confounders 31 could be considered in conjunction.…”

MicroRNA-219c-5p regulates bladder smooth muscle cell fibrosis by targeting FN1

“…Anti brotic therapy may be an effective way to control bladder dysfunction, but it has not been well studied. [15][16][17] Fibronectin is an extracellular macromolecular membrane protein present on the surface of animal cells and is the main noncollagen glycoprotein in the ECM and basement membrane. It is also very abundant in the ECM of various tumors, including osteosarcoma, leiomyosarcoma, and gastric cancer.…”