Potential Urinary Protein Biomarker Candidates for the Accurate Detection of Prostate Cancer among Benign Prostatic Hyperplasia Patients

Abstract

Globally, Prostate cancer (PCa) is the most frequently occurring non-cutaneous cancer, and is the second highest cause of cancer mortality in men. Serum prostate specific antigen (PSA) has been the standard in PCa screening since its approval by the American Food & Drug Administration (FDA) in 1994. Currently, PSA is used as an indicator for PCa - patients with a serum PSA level above 4ng/mL will often undergo prostate biopsy to confirm cancer. Unfortunately fewer than ~30% of these men will biopsy positive for cancer, meaning that the majority of men undergo invasive biopsy with little benefit. Despite PSA's notoriously poor specificity (33%), there is still a significant lack of credible alternatives. Therefore an ideal biomarker that can specifically detect PCa at an early stage is urgently required. The aim of this study was to investigate the potential of using deregulation of urinary proteins in order to detect Prostate Cancer (PCa) among Benign Prostatic Hyperplasia (BPH). To identify the protein signatures specific for PCa, protein expression profiling of 8 PCa patients, 12 BPH patients and 10 healthy males was carried out using LC-MS/MS. This was followed by validating relative expression levels of proteins present in urine among all the patients using quantitative real time-PCR. This was followed by validating relative expression levels of proteins present in urine among all the patients using quantitative real time-PCR. This approach revealed that significant the down-regulation of Fibronectin and TP53INP2 was a characteristic event among PCa patients. Fibronectin mRNA down-regulation, was identified as offering improved specificity (50%) over PSA, albeit with a slightly lower although still acceptable sensitivity (75%) for detecting PCa. As for TP53INP2 on the other hand, its down-regulation was moderately sensitive (75%), identifying many patients with PCa, but was entirely non-specific (7%), designating many of the benign samples as malignant and being unable to accurately identify more than one negative.

Detection of aggressive prostate cancer associated glycoproteins in urine using glycoproteomics and mass spectrometry

“…Proteomics provides a powerful means to examine the whole proteome or subproteomes in different disease conditions . The majority of extracellular proteins, including cell surface, transmembrane, and secreted proteins, are modified by glycans, and therefore referred to as glycoproteins.…”

MicroRNAs as potential biomarkers to predict the risk of urinary retention following intradetrusor onabotulinumtoxin‐A injection

“…Diagnostic and/or prognostic novel biomarkers are highly desirable to help better predict which patients will develop urinary retention. Our present investigation was prompted by studies demonstrating the potential of miR expression to convey outcome specific information owing to their ability to regulate the transcriptome . We studied 13 miR species known for their effect on neurotrophin expression and smooth muscle function, and we demonstrated the potential of two miRs (miR125b and miR 221) to assess the risk of urinary retention after onaBoNT‐A injection in OAB patients.…”

“…Mid‐stream urine samples were collected in urine tube containing preservative (Cat# 1811; Norgen Biotek®, Thorold, ON, Canada) at baseline and again at 3 weeks after onaBoNT‐A injection . NGF levels in urine samples were analyzed using Chemikine™ Nerve Growth Factor (NGF) ELISA Kit (Millipore, Billerica, MA, Cat # CYT304).…”

Proteomics in Diagnosis of Prostate Cancer/ Протеомика Во Дијагноза На Простатниот Карцином

“…Another study aiming to identify the protein signatures specific for PCa was carried out using LC-MS/MS. Protein expression profiling of urine proteome of 8 PCa patients, 12 BPH patients and 10 healthy males revealed significant down-regulation of fibronectin (FN) and TP53INP2 in PCa patients [95]. The validation results pointed out FN as a potential biomarker with 50% specificity and 75% sensitivity for PCa.…”