Approaches to the discovery of non-invasive urinary biomarkers of prostate cancer

Abstract

Prostate cancer (PCa) continues to be one of the most common cancers in men worldwide. Prostate specific antigen (PSA) measured in blood has been used for decades as an aid for physicians to detect the presence of prostate cancer. However, the PSA test has limited sensitivity and specificity, leading to unnecessary biopsies, overdiagnosis and overtreatment of patients. For these reasons, there is an urgent need for more accurate PCa biomarkers that can detect PCa with high sensitivity and specificity. Urine is a unique source of potential protein biomarkers that can be measured in a non-invasive way. This review comprehensively summarizes state of the art approaches used in the discovery and validation of urinary biomarkers for PCa. Numerous strategies are currently being used in the discovery of urinary biomarkers for prostate cancer including gel-based separation techniques, mass spectrometry, activity-based proteomic assays and software approaches. Antibody-based approaches remain preferred method for validation of candidate biomarkers with rapidly advancing multiplex immunoassays and MS-based targeted approaches. In the last decade, there has been a dramatic acceleration in the development of new techniques and approaches in the discovery of protein biomarkers for prostate cancer including computational, statistical and data mining methods. Many urinary-based protein biomarkers have been identified and have shown significant promise in initial studies. Examples of these potential biomarkers and the methods utilized in their discovery are also discussed in this review.

CD5L as an Extracellular Vesicle-Derived Biomarker for Liquid Biopsy of Lung Cancer

“…Top-down proteomics involves the separation of intact proteins without enzymatic treatment and then the proteins are subjected to tandem mass spectroscopy (MS/MS). Alternatively, the bottom-up approach involves the chemical or enzymatic digestion of proteins into smaller peptides, followed by matrix-assisted laser desorption ionization–time-of-flight mass spectroscopy (MALDI–TOF/MS) [ 11 ]. The top-down approach provides the advantage of reduced sample complexity, while resolving isoforms, spliced variants, and post-translationally modified (PTM) proteins in a given sample [ 12 ].…”

Proteomic Landscape of Prostate Cancer: The View Provided by Quantitative Proteomics, Integrative Analyses, and Protein Interactomes

“…Proteomics in biomarker discovery aiming for improved disease management of prostate cancer have recently been excellently reviewed by others [ 36 , 37 , 38 ]. Proteomic efforts to identify biomarkers from body fluids and vesicles have also been reviewed elsewhere [ 39 , 40 , 41 , 42 , 43 ].…”

LMTK2 as Potential Biomarker for Stratification between Clinically Insignificant and Clinically Significant Prostate Cancer

“…Due to blood-based biomarkers low risks to the patient and easy access, it represents one of the most attractive methods for the diagnostic evaluation. Personalized molecular screening of noninvasive biomarkers may help identify patients with clinically insignificant prostate cancer in a cost-effective and noninvasive manner [ 34 ].…”