Abstract

Molecular diagnostics based on discovery research holds the promise of improving screening methods for prostate cancer (PCa). Furthermore, the congregated information prompts the question whether the urinary extracellular vesicles (uEV) proteome has been thoroughly explored, especially at the proteome level. In fact, most extracellular vesicles (EV) based biomarker studies have mainly targeted plasma or serum. Therefore, in this study, we aim to inquire about possible strategies for urinary biomarker discovery particularly focused on the proteome of urine EVs. Proteomics data deposited in the PRIDE archive were reanalyzed to target identifications of potential PCa markers. Network analysis of the markers proposed by different prostate cancer studies revealed moderate overlap. The recent throughput improvements in mass spectrometry together with the network analysis performed in this study, suggest that a larger standardized cohort may provide potential biomarkers that are able to fully characterize the heterogeneity of PCa. According to our analysis PCa studies based on urinary EV proteome presents higher protein coverage compared to plasma, plasma EV, and voided urine proteome. This together with a direct interaction of the prostate gland and urethra makes uEVs an attractive option for protein biomarker studies. In addition, urinary proteome based PCa studies must also evaluate samples from bladder and renal cancers to assess specificity for PCa.

Highlights

  • Prostate cancer (PCa) is mostly an asymptomatic and slowly growing tumor, which might start developing in young men, but is typically only possible to start detecting around the age of 40–50 with an average age of about 66 years [1]

  • In-depth research has been conducted towards the discovery of new biomarkers for diagnosis and prognosis of prostate cancer (PCa) due to the inability of current biomarkers to accurately predict disease aggressiveness

  • mass spectrometry (MS)-based proteomics enables large scale and deep profiling of urinary extracellular vesicles (uEV) proteomes, which reflect the cellular processes associated with tissue-of-origin, creating new biological insights on PCa

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Summary

Introduction

Prostate cancer (PCa) is mostly an asymptomatic and slowly growing tumor, which might start developing in young men, but is typically only possible to start detecting around the age of 40–50 with an average age of about 66 years [1]. Alascksuocfha, tshpeeclaifickc mofaarkspere(csi)fifcomr PaCrkaerd(isa)gfnoor sPiCs wa ditihaacganpoasciistywtiothdaisctainpgaucitsyhtiondioslteingt ufrioshminadgoglreenstsifvroemdiasegagsreslseiavdesdtioseuansenelecaedssatroyupnrnoesctaestebisoaprysipesroasntadteubninoepcseiessaarnydtruenantmecensstas.ryFutrretahtemrmenotsre. ,Faurstuhbesrmetoorfec, lainsuicbaslelyt osfigcnliinfiicanllyt PsiCga(cnsPifCica)nwt PilCl abe(clsePftCuan) dweitlel cbteedlef[t7]u.ndetected [7]

Diagnostic Methods
Summary
Exosome Biogenesis
Current Diagnostic Methods and Advantages of Using Liquid Biopsies
Proteomics in PCa
Proteins Identified in PCa Proteomics Studies
Comparing uEV Proteins from Different MS-Based Studies
Findings
Conclusions and Future Perspectives
Full Text
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