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Diagnostic Biomarkers in Prostate Cancer 2020

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A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 36885

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Prof. Dr. Jochen Neuhaus

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Department of Urology, Research Laboratory, University of Leipzig, Leipzig, Germany
Interests: improving the diagnosis of prostate cancer, bladder cancer and other urologic diseases by development of biomarkers; proteomics; NMR-metabolomics; understanding of molecular mechanisms of receptor signaling and trafficking; elucidating the role of the tumor microenvironment; improvement of minimal invasive focal therapies and immune response priming in urologic cancers
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Dear Colleagues,

Prostate cancer (PCa) is the second most common cancer in men, worldwide, ranking first in more-developed regions and second (behind lung cancer) in less-developed regions. There are considerable variations in incidence and mortality rates in different countries and populations. Despite all efforts, mortality is still high and about one patient in 39 will die of PCa. Detection of PCa and clinical decision making mostly relies on clinical examination and PSA-levels, followed by invasive biopsy where indicated. However, known limitations of PSA diagnostics and the health risks of biopsy taking require more reliable biomarkers to diagnose PCa in first place, stratify for indolent and aggressive tumors in second place and finally allowing non-invasive monitoring of disease development and treatment effects.

This special issue aims to comprehensively cover all aspects of novel PCa biomarker development and validation with special emphasis on new approaches and adaptation of biomarkers to population peculiarities. We also invite manuscripts elucidating the molecular background of biomarkers. Original work, as well as reviews, are welcome.

Thank you for your consideration.

Prof. Dr. Jochen Neuhaus
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

prostate cancer biomarkers
diagnostic, stratification and monitoring
metabolomics
proteomics
genetics
epidemiology

Published Papers (12 papers)

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Editorial

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3 pages, 168 KiB

Open AccessEditorial

Special Issue “Diagnostic Biomarkers in Prostate Cancer 2020”

by Jochen Neuhaus

Diagnostics 2021, 11(3), 505; https://doi.org/10.3390/diagnostics11030505 - 12 Mar 2021

Cited by 1 | Viewed by 1287

Abstract

The search for novel prostate cancer biomarkers is one of the major topics in recent urologic research [...] Full article

(This article belongs to the Special Issue Diagnostic Biomarkers in Prostate Cancer 2020)

Research

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18 pages, 3003 KiB

Open AccessArticle

Novel Metabolic Signatures of Prostate Cancer Revealed by ¹H-NMR Metabolomics of Urine

by Bo Yang, Chuan Zhang, Sheng Cheng, Gonghui Li, Jan Griebel and Jochen Neuhaus

Diagnostics 2021, 11(2), 149; https://doi.org/10.3390/diagnostics11020149 - 20 Jan 2021

Cited by 19 | Viewed by 3463

Abstract

Prostate cancer (PC) is one of the most common male cancers worldwide. Until now, there is no consensus about using urinary metabolomic profiling as novel biomarkers to identify PC. In this study, urine samples from 50 PC patients and 50 non-cancerous individuals (control group) were collected. Based on ¹H nuclear magnetic resonance (¹H-NMR) analysis, 20 metabolites were identified. Subsequently, principal component analysis (PCA), partial least squares-differential analysis (PLS-DA) and ortho-PLS-DA (OPLS-DA) were applied to find metabolites to distinguish PC from the control group. Furthermore, Wilcoxon test was used to find significant differences between the two groups in metabolite urine levels. Guanidinoacetate, phenylacetylglycine, and glycine were significantly increased in PC, while L-lactate and L-alanine were significantly decreased. The receiver operating characteristics (ROC) analysis revealed that the combination of guanidinoacetate, phenylacetylglycine, and glycine was able to accurately differentiate 77% of the PC patients with sensitivity = 80% and a specificity = 64%. In addition, those three metabolites showed significant differences in patients stratified for Gleason score 6 and Gleason score ≥7, indicating potential use to detect significant prostate cancer. Pathway enrichment analysis using the KEGG (Kyoto Encyclopedia of Genes and Genomes) and the SMPDB (The Small Molecule Pathway Database) revealed potential involvement of KEGG “Glycine, Serine, and Threonine metabolism” in PC. The present study highlights that guanidinoacetate, phenylacetylglycine, and glycine are potential candidate biomarkers of PC. To the best knowledge of the authors, this is the first study identifying guanidinoacetate, and phenylacetylglycine as potential novel biomarkers in PC. Full article

(This article belongs to the Special Issue Diagnostic Biomarkers in Prostate Cancer 2020)

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15 pages, 1145 KiB

Open AccessArticle

Xanthine Oxidase/Dehydrogenase Activity as a Source of Oxidative Stress in Prostate Cancer Tissue

by Andrej Veljković, Jovan Hadži-Dokić, Dušan Sokolović, Dragoslav Bašić, Ljubinka Veličković-Janković, Marko Stojanović, Dejan Popović and Gordana Kocić

Diagnostics 2020, 10(9), 668; https://doi.org/10.3390/diagnostics10090668 - 03 Sep 2020

Cited by 13 | Viewed by 3094

Abstract

Prostate cancer (PC) is one of the most frequent malignancies. Better biomarkers are constantly wanted, such as those which can help with the prediction of cancer behavior. What is also needed is a marker which may serve as a possible therapeutic target. Oxidative stress (OS), which is a hallmark of cancer, is included in the pathogenesis and progression of PC. We have conducted the present study to determine whether xanthine oxidase/dehydrogenase activity is the source of OS in prostate tissue. We have also determined the concentration of TBA-reactive substances (TBARS) and advanced oxidation protein products (AOPP), as well as the activity of catalase. Xanthine oxidase (XO) activity is significantly higher (p < 0.001) in tumor tissue when compared to the control healthy tissue. The concentration of TBARS (p < 0.001) and AOPP (p < 0.05) are also higher in tumor tissue. Catalase has raised its activity (p < 0.05) versus the control. There is also a strong correlation between XO activity and prostate-specific antigen (PSA) levels in the serum. These results indicate a significant role of XO activity in OS in prostate carcinogenesis, and it could be a possible theranostic biomarker, which can be important for a better understanding of the disease, its evolution, and prognosis. A promising treatment may be using XO inhibitors such as allopurinol as adjuvant therapy. Full article

(This article belongs to the Special Issue Diagnostic Biomarkers in Prostate Cancer 2020)

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20 pages, 3547 KiB

Open AccessArticle

Molecular Changes in Tissue Proteome during Prostate Cancer Development: Proof-of-Principle Investigation

by Agnieszka Latosinska, Katarina Davalieva, Manousos Makridakis, William Mullen, Joost P. Schanstra, Antonia Vlahou, Harald Mischak and Maria Frantzi

Diagnostics 2020, 10(9), 655; https://doi.org/10.3390/diagnostics10090655 - 31 Aug 2020

Cited by 11 | Viewed by 2950

Abstract

(1) Background: Prostate cancer (PCa) is characterized by high heterogeneity. The aim of this study was to investigate molecular alterations underlying PCa development based on proteomics data. (2) Methods: Liquid chromatography coupled to tandem mass spectrometry was conducted for 22 fresh-frozen tissue specimens from patients with benign prostatic hyperplasia (BPH, n = 5) and PCa (n = 17). Mann Whitney test was used to define significant differences between the two groups. Association of protein abundance with PCa progression was evaluated using Spearman correlation, followed by verification through investigating the Prostate Cancer Transcriptome Atlas. Functional enrichment and interactome analysis were carried out using Metascape and String. (3) Results: Proteomics analysis identified 1433 proteins, including 145 proteins as differentially abundant between patients with PCa and BPH. In silico analysis revealed alterations in several pathways and hallmarks implicated in metabolism and signalling, represented by 67 proteins. Among the latter, 21 proteins were correlated with PCa progression at both the protein and mRNA levels. Interactome analysis of these 21 proteins predicted interactions between Myc proto-oncogene (MYC) targets, protein processing in the endoplasmic reticulum, and oxidative phosphorylation, with MYC targets having a central role. (4) Conclusions: Tissue proteomics allowed for characterization of proteins and pathways consistently affected during PCa development. Further validation of these findings is required. Full article

(This article belongs to the Special Issue Diagnostic Biomarkers in Prostate Cancer 2020)

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17 pages, 2153 KiB

Open AccessArticle

The Influence of Radical Prostatectomy on the Expression of Cell-Free MiRNA

by Maria Yu. Konoshenko, Olga E. Bryzgunova, Evgeniy A. Lekchnov, Evgeniya V. Amelina, Sergey V. Yarmoschuk, Svetlana V. Pak and Pavel P. Laktionov

Diagnostics 2020, 10(8), 600; https://doi.org/10.3390/diagnostics10080600 - 17 Aug 2020

Cited by 13 | Viewed by 2547

Abstract

MiRNAs of blood and urine have been shown to represent a convenient source of biomarkers for prostate cancer (PCa) diagnosis and assessment of the therapy effectiveness due to their high stability and representation and the low invasiveness of sample collection. Here, we studied the influence of radical prostatectomy (RP) on the expression of 12 cell-free miRNAs previously shown as potential markers of PCa (i.e., miR-19b, miR-22, miR-92a, miR-378, miR-425, miR-30e, miR-31, miR-125b, miR-200b, miR-205, miR-375 and miR-660). The relative expression of the miRNAs combined into 31 paired ratios was evaluated in the urine extracellular vesicles (EVs), clarified urine (CU) and blood plasma of healthy donors, pre- and post-RP samples of PCa patients. Nineteen miRNA ratios based on combinations of ten of the miRNAs (miR-19b, miR-30e, miR-31, miR-125b, miR-200b, miR-205, miR-375, miR-378, miR-425, and miR-660) were altered by RP. The comparative expression analysis of the cell-free miRNA ratios between healthy donors and PCa patients revealed miR-125b/miR-30e and miR-375/miR-30e as potential markers for evaluating therapeutic efficacy. MiR-378/miR-19b, miR-425/miR-19b, miR-200/miR-30e, miR-660/miR-30e, and miR-205/miR-30e had minor prognostic value but could be used to increase the steadiness of the diagnostic system. The urine EVs had the highest potential as a source of markers. Full article

(This article belongs to the Special Issue Diagnostic Biomarkers in Prostate Cancer 2020)

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18 pages, 1107 KiB

Open AccessArticle

Evaluation of MicroRNAs as Non-Invasive Diagnostic Markers in Urinary Cells from Patients with Suspected Prostate Cancer

by Angelika Borkowetz, Andrea Lohse-Fischer, Jana Scholze, Ulrike Lotzkat, Christian Thomas, Manfred P. Wirth, Susanne Fuessel and Kati Erdmann

Diagnostics 2020, 10(8), 578; https://doi.org/10.3390/diagnostics10080578 - 09 Aug 2020

Cited by 16 | Viewed by 2564

Abstract

Currently used tumor markers for early diagnosis of prostate cancer (PCa) are often lacking sufficient specificity and sensitivity. Therefore, the diagnostic potential of selected microRNAs in comparison to serum PSA levels and PSA density (PSAD) was explored. A panel of 12 PCa-associated microRNAs was quantified by qPCR in urinary sediments from 50 patients with suspected PCa undergoing prostate biopsy, whereupon PCa was detected in 26 patients. Receiver operating characteristic (ROC) curve analyses revealed a potential for non-invasive urine-based PCa detection for miR-16 (AUC = 0.744, p = 0.012; accuracy = 76%) and miR-195 (AUC = 0.729, p = 0.017; accuracy = 70%). While serum PSA showed an insufficient diagnostic value (AUC = 0.564, p = 0.656; accuracy = 50%) in the present cohort, PSAD displayed an adequate diagnostic performance (AUC = 0.708, p = 0.031; accuracy = 70%). Noteworthy, the combination of PSAD with the best candidates miR-16 and miR-195 either individually or simultaneously improved the diagnostic power (AUC = 0.801–0.849, p < 0.05; accuracy = 76–90%). In the sub-group of patients with PSA ≤ 10 ng/mL (n = 34), an inadequate diagnostic power of PSAD alone (AUC = 0.595, p = 0.524; accuracy = 68%) was markedly surpassed by miR-16 and miR-195 individually as well as by their combination with PSAD (AUC = 0.772–0.882, p < 0.05; accuracy = 74–85%). These findings further highlight the potential of urinary microRNAs as molecular markers with high clinical performance. Overall, these results need to be validated in a larger patient cohort. Full article

(This article belongs to the Special Issue Diagnostic Biomarkers in Prostate Cancer 2020)

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13 pages, 1622 KiB

Open AccessArticle

Utilization of Multiparametric MRI of Prostate in Patients under Consideration for or Already in Active Surveillance: Correlation with Imaging Guided Target Biopsy

by Jinxing Yu, Ann S. Fulcher, Sarah Winks, Mary A. Turner, William Behl, Anna Lee Ware, Nitai D. Mukhopadhyay, Candice Kim, Christopher Jackson, Harnek S. Bajaj and Lance J. Hampton

Diagnostics 2020, 10(7), 441; https://doi.org/10.3390/diagnostics10070441 - 29 Jun 2020

Cited by 2 | Viewed by 2331

Abstract

This study sought to assess the value of multiparametric magnetic resonance image (mp-MRI) in patients with a prostate cancer (PCa) Gleason score of 6 or less under consideration for or already in active surveillance and to determine the rate of upgrading by target biopsy. Three hundred and fifty-four consecutive men with an initial transrectal ultrasound-guided (TRUS) biopsy-confirmed PCa Gleason score of 6 or less under clinical consideration for or already in active surveillance underwent mp-MRI and were retrospectively reviewed. One hundred and nineteen of 354 patients had cancer-suspicious regions (CSRs) at mp-MRI. Each CSR was assigned a Prostate Imaging Reporting and Data System (PI-RADS) score based on PI-RADS v2. One hundred and eight of 119 patients underwent confirmatory imaging-guided biopsy for CSRs. Pathology results including Gleason score (GS) and percentage of specimens positive for PCa were recorded. Associations between PI-RADS scores and findings at target biopsy were evaluated using logistic regression. At target biopsy, 81 of 108 patients had PCa (75%). Among them, 77 patients had upgrading (22%, 77 of 354 patients). One hundred and forty-six CSRs in 108 patients had PI-RADS 3 n = 28, 4 n = 66, and 5 n = 52. The upgraded rate for each category of CSR was for PI-RADS 3 (5 of 28, 18%), 4 (47 of 66, 71%) and 5 (49 of 52, 94%). Using logistic regression analysis, differences in PI-RADS scores from 3 to 5 are significantly associated with the probability of disease upgrade (20%, 73%, and 96% for PI-RADS score of 3, 4, and 5, respectively). Adding mp-MRI to patients under consideration for or already in active surveillance helps to identify undiagnosed PCa of a higher GS or higher volume resulting in upgrading in 22%. Full article

(This article belongs to the Special Issue Diagnostic Biomarkers in Prostate Cancer 2020)

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13 pages, 909 KiB

Open AccessArticle

Profiling of Circulating microRNAs in Prostate Cancer Reveals Diagnostic Biomarker Potential

by Jacob Fredsøe, Anne K. I. Rasmussen, Peter Mouritzen, Marianne T. Bjerre, Peter Østergren, Mikkel Fode, Michael Borre and Karina D. Sørensen

Diagnostics 2020, 10(4), 188; https://doi.org/10.3390/diagnostics10040188 - 28 Mar 2020

Cited by 20 | Viewed by 3322

Abstract

Early detection of prostate cancer (PC) is paramount as localized disease is generally curable, while metastatic PC is generally incurable. There is a need for improved, minimally invasive biomarkers as current diagnostic tools are inaccurate, leading to extensive overtreatment while still missing some clinically significant cancers. Consequently, we profiled the expression levels of 92 selected microRNAs by RT-qPCR in plasma samples from 753 patients, representing multiple stages of PC and non-cancer controls. First, we compared plasma miRNA levels in patients with benign prostatic hyperplasia (BPH) or localized prostate cancer (LPC), versus advanced prostate cancer (APC). We identified several dysregulated microRNAs with a large overlap of 59 up/down-regulated microRNAs between BPH versus APC and LPC versus APC. Besides identifying several novel PC-associated dysregulated microRNAs in plasma, we confirmed the previously reported upregulation of miR-375 and downregulation of miR-146a-5p. Next, by randomly splitting our dataset into a training and test set, we identified and successfully validated a novel four microRNA diagnostic ratio model, termed bCaP (miR-375*miR-33a-5p/miR-16-5p*miR-409-3p). Combined in a model with prostate specific antigen (PSA), digital rectal examination status, and age, bCaP predicted the outcomes of transrectal ultrasound (TRUS)-guided biopsies (negative vs. positive) with greater accuracy than PSA alone (Training: area under the curve (AUC), model = 0.84; AUC, PSA = 0.63. Test set: AUC, model = 0.67; AUC, PSA = 0.56). It may be possible in the future to use this simple and minimally invasive bCaP test in combination with existing clinical parameters for a more accurate selection of patients for prostate biopsy. Full article

(This article belongs to the Special Issue Diagnostic Biomarkers in Prostate Cancer 2020)

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11 pages, 2657 KiB

Open AccessArticle

Oxidative Stress and Antioxidant Status in High-Risk Prostate Cancer Subjects

by Sanjeev Shukla, Janmejai K. Srivastava, Eswar Shankar, Rajnee Kanwal, Akbar Nawab, Haripaul Sharma, Natarajan Bhaskaran, Lee E. Ponsky, Pingfu Fu, Gregory T. MacLennan and Sanjay Gupta

Diagnostics 2020, 10(3), 126; https://doi.org/10.3390/diagnostics10030126 - 27 Feb 2020

Cited by 38 | Viewed by 3712

Abstract

The oxidant/antioxidant balance has been implicated in the pathophysiology of prostate cancer. We investigated oxidative damage and antioxidant status in high-risk prostate cancer subjects. Reduced glutathione (GSH) levels were measured in erythrocytes, 8-hydroxydeoxyguanosine (8-OHdG) in leukocytes and plasma levels of catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GSH-R), glutathione S-transferase (GST), superoxide dismutase (SOD), and lipid peroxide products were measured in high-risk and age-matched healthy subjects. Serum PSA levels were significantly higher (p < 0.0001) in high-risk subjects, whereas GST (p < 0.0001) and GSH (p < 0.002) were higher in healthy controls. Levels of 8-OHdG, an oxidized nucleoside of DNA, were significantly increased (p < 0.0001) in high-risk subjects. No marked difference in the levels of CAT (p = 0.237), GSH-Px (p = 0.74), GSH-R (p = 0.344), SOD (p = 0.109), and lipid peroxide products (p = 0129) were observed between two groups. Pearson’s correlation between GST and PSA (r = −0.69 (p < 0.0001)), GST and 8-OHdG (r = −0.62 (p < 0.0004)), GSH and 8-OHdG (r= −0.39 (p = 0.038)), and CAT and GSH-Px (r= −0.33 (p = 0.04)) were found to be negatively correlated, whereas 8-OHdG and PSA were positively associated (r= 0.57 (p < 0.002). These results indicate a significant role of oxidative damage in prostate carcinogenesis, particularly during the early stages of development. In conclusion, our data support the importance of antioxidant defense as a valuable diagnostic and/or prognostic marker in prostate cancer. Full article

(This article belongs to the Special Issue Diagnostic Biomarkers in Prostate Cancer 2020)

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17 pages, 804 KiB

Open AccessArticle

The Panel of 12 Cell-Free MicroRNAs as Potential Biomarkers in Prostate Neoplasms

by Maria Yu. Konoshenko, Evgeniy A. Lekchnov, Olga E. Bryzgunova, Ivan A. Zaporozhchenko, Sergey V. Yarmoschuk, Oksana A. Pashkovskaya, Svetlana V. Pak and Pavel P. Laktionov

Diagnostics 2020, 10(1), 38; https://doi.org/10.3390/diagnostics10010038 - 10 Jan 2020

Cited by 23 | Viewed by 3340

Abstract

Prostate cancer is a global biological, medical, and social issue aggravated by the lack of reliable, highly specific, and sensitive non-invasive tests for diagnosis and staging of prostate cancer. One prospective source of biomarkers are the cell-free miRNAs present in various biological fluids. In the present study, we validated the diagnostic potential of cell-free miRNAs: miR-19b, miR-22, miR-92a, miR-378, miR-425, miR-30e, miR-31, miR-125b, miR-200b, miR-205, miR-375, and miR-660; we estimated the required sample size and the minimal miRNA set for a subsequent large-scale validation study. Relative expression of 12 miRNA combined in 31 ratios was investigated in three fractions of biological fluids (urine extracellular vesicles, clarified urine, and plasma) obtained from patients with prostate cancer (n = 10), benign prostate hyperplasia (n = 8), and healthy volunteers (n = 11). Eight of the miRNAs found in urine vesicles (miR-19b, miR-30e, miR-31, miR-92a, miR-125, miR-200, miR-205, and miR-660) showed great promise and when combined into six ratios (miR-125b/miR-30e, miR-200/miR-30e, miR-205/miR-30e, miR-31/miR-30e, miR-660/miR-30e, and miR-19b/miR-92a) could classify patients with prostate cancer, benign prostate hyperplasia, and healthy donors with 100% specificity, 100% sensitivity, and with a high degree of reliability for most donors. Full article

(This article belongs to the Special Issue Diagnostic Biomarkers in Prostate Cancer 2020)

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Review

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20 pages, 1372 KiB

Open AccessReview

Omics Derived Biomarkers and Novel Drug Targets for Improved Intervention in Advanced Prostate Cancer

by Maria Frantzi, Marie C. Hupe, Axel S. Merseburger, Joost P. Schanstra, Harald Mischak and Agnieszka Latosinska

Diagnostics 2020, 10(9), 658; https://doi.org/10.3390/diagnostics10090658 - 31 Aug 2020

Cited by 8 | Viewed by 3497

Abstract

Prostate cancer (PCa) is one of the most frequently diagnosed malignancies, and the fifth leading cause of cancer related mortality in men. For advanced PCa, radical prostatectomy, radiotherapy, and/or long-term androgen deprivation therapy are the recommended treatment options. However, subsequent progression to metastatic disease after initial therapy results in low 5-year survival rates (29%). Omics technologies enable the acquisition of high-resolution large datasets that can provide insights into molecular mechanisms underlying PCa pathology. For the purpose of this article, a systematic literature search was conducted through the Web of Science Database to critically evaluate recent omics-driven studies that were performed towards: (a) Biomarker development and (b) characterization of novel molecular-based therapeutic targets. The results indicate that multiple omics-based biomarkers with prognostic and predictive value have been validated in the context of PCa, with several of those being also available for commercial use. At the same time, omics-driven potential drug targets have been investigated in pre-clinical settings and even in clinical trials, holding the promise for improved clinical management of advanced PCa, as part of personalized medicine pipelines. Full article

(This article belongs to the Special Issue Diagnostic Biomarkers in Prostate Cancer 2020)

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10 pages, 397 KiB

Open AccessReview

An Update on the Prognostic and Predictive Serum Biomarkers in Metastatic Prostate Cancer

by Helen Saxby, Christos Mikropoulos and Stergios Boussios

Diagnostics 2020, 10(8), 549; https://doi.org/10.3390/diagnostics10080549 - 31 Jul 2020

Cited by 38 | Viewed by 3701

Abstract

Serum biomarkers are molecules produced by normal and abnormal cells. Prostate specific antigen (PSA) is an example of a serum biomarker used widely in the diagnosis and prognostication of prostate cancer. PSA has its limitations as it is organ- but not cancer-specific. The aim of this review is to summarize the current published data on the potential prognostic and predictive biomarkers in metastatic prostate cancer (mPC) that can be used in conjunction with PSA. These biomarkers include microRNAs, androgen receptor variants, bone metabolism, neuroendocrine and metabolite biomarkers, and could guide treatment selection and sequence in an era where we strive to personalized therapy. Full article

(This article belongs to the Special Issue Diagnostic Biomarkers in Prostate Cancer 2020)

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