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.
Highlights
Prostate cancer (PCa) is the most prevalent cancer in males and it is estimated that approximately 116, 000 men living in USA were diagnosed with prostate cancer in 2017 [1]
We found that urinary matrix metalloproteinases (MMP) levels were higher in patients with local-regional cancer compared with normal controls
Urine based biomarkers offer the potential for home testing which would facilitate diagnosis and monitoring of prostate cancer patients
Summary
Prostate cancer (PCa) is the most prevalent cancer in males and it is estimated that approximately 116, 000 men living in USA were diagnosed with prostate cancer in 2017 [1]. These proteins, either alone or when multiplexed, showed www.oncotarget.com significant sensitivity and specificity in discriminating between patients with BPH and those with localized prostate cancer These new biomarkers significantly increased predictive accuracy based on PSA categories from 0.734 to 0.812 when combined (P=0.004, Delong test for comparing ROC curves) [5]. Another commonly used method to validate urinary protein biomarkers is western blot (immunoblot) analysis This approach can be used only on small cohorts due to its limitations regarding detection of single antigens, the requirement to optimize experimental conditions, labor intensity, lack of specific antibodies and lack of high-throughput capacity among other limitations.
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