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Special Issue "Diagnostic, Prognostic and Predictive Biomarkers in Prostate Cancer 2018"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 31 August 2019

Special Issue Editors

Guest Editor
Prof. Dr. Carsten Stephan

Department of Urology, Charité-Universitätsmedizin Berlin, Germany
E-Mail
Phone: +49 30 450 515 052
Fax: +49 30 450 515 904
Interests: biomarkers of prostate cancer; artificial neural networks; prostate health index
Guest Editor
Prof. Klaus Jung

Department of Urology, Charité University Hospital, 10117 Berlin, Germany
E-Mail
Interests: clinical biochemistry; molecular and biochemical urooncology; RNA and DNA biology; general laboratory medicine

Special Issue Information

Dear Colleagues,

Prostate cancer is the most common cancer in men in the Western world. Therefore, its early diagnosis, which is mainly based on serum prostate-specific antigen (PSA), has especially gained attention in several fields of research. New biomarkers in serum and urine have been described; for example, the prostate health index (PHI) or urinary Prostate cancer gene 3 (PCA3), or others, including several biomarker-based multivariate models. However, not only the diagnosis, but also, more so, the prognosis or further prediction of this very common disease is important to know. Here, several new nucleic acid or protein-based tissue biomarkers have been described. As already described for other types of cancer, individualized medicine, such as theranostics, a combination of diagnostics and therapeutics, has been a new attraction for late stage prostate cancer, including castration resistant prostate cancer. This Special Issue focuses on “Diagnostic, Prognostic and Predictive Biomarkers in Prostate Cancer”.

We warmly welcome submissions, including original papers and reviews, on this widely-discussed topic.

Prof. Carsten Stephan
Prof. Klaus Jung
Guest Editors

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 papers will be 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. International Journal of Molecular Sciences 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 1800 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

  • Urinary biomarkers on prostate cancer
  • Serum/plasma biomarkers
  • Tissue biomarkers (nuleic acid/protein-based)
  • Prognostic factors
  • Multivariate models

Related Special Issue

Published Papers (12 papers)

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Research

Jump to: Review

Open AccessArticle
Glycidamide Promotes the Growth and Migratory Ability of Prostate Cancer Cells by Changing the Protein Expression of Cell Cycle Regulators and Epithelial-to-Mesenchymal Transition (EMT)-Associated Proteins with Prognostic Relevance
Int. J. Mol. Sci. 2019, 20(9), 2199; https://doi.org/10.3390/ijms20092199
Received: 31 March 2019 / Revised: 25 April 2019 / Accepted: 1 May 2019 / Published: 4 May 2019
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Abstract
Acrylamide (AA) and glycidamide (GA) can be produced in carbohydrate-rich food when heated at a high temperature, which can induce a malignant transformation. It has been demonstrated that GA is more mutagenic than AA. It has been shown that the proliferation rate of [...] Read more.
Acrylamide (AA) and glycidamide (GA) can be produced in carbohydrate-rich food when heated at a high temperature, which can induce a malignant transformation. It has been demonstrated that GA is more mutagenic than AA. It has been shown that the proliferation rate of some cancer cells are increased by treatment with GA; however, the exact genes that are induced by GA in most cancer cells are not clear. In the present study, we demonstrated that GA promotes the growth of prostate cancer cells through induced protein expression of the cell cycle regulator. In addition, we also found that GA promoted the migratory ability of prostate cancer cells through induced epithelial-to-mesenchymal transition (EMT)-associated protein expression. In order to understand the potential prognostic relevance of GA-mediated regulators of the cell cycle and EMT, we present a three-gene signature to evaluate the prognosis of prostate cancer patients. Further investigations suggested that the three-gene signature (CDK4, TWIST1 and SNAI2) predicted the chances of survival better than any of the three genes alone for the first time. In conclusion, we suggested that the three-gene signature model can act as marker of GA exposure. Hence, this multi-gene panel may serve as a promising outcome predictor and potential therapeutic target in prostate cancer patients. Full article
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Open AccessArticle
rs4143815-PDL1, a New Potential Immunogenetic Biomarker of Biochemical Recurrence in Locally Advanced Prostate Cancer after Radiotherapy
Int. J. Mol. Sci. 2019, 20(9), 2082; https://doi.org/10.3390/ijms20092082
Received: 18 March 2019 / Revised: 19 April 2019 / Accepted: 25 April 2019 / Published: 27 April 2019
PDF Full-text (1233 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Up to 30–50% of patients with locally advanced prostate cancer (PCa) undergoing radiotherapy (RT) experience biochemical recurrence (BCR). The immune system affects the RT response. Immunogenetics could define new biomarkers for personalization of PCa patients’ treatment. The aim of this study is to [...] Read more.
Up to 30–50% of patients with locally advanced prostate cancer (PCa) undergoing radiotherapy (RT) experience biochemical recurrence (BCR). The immune system affects the RT response. Immunogenetics could define new biomarkers for personalization of PCa patients’ treatment. The aim of this study is to define the immunogenetic biomarkers of 10 year BCR (primary aim), 10 year overall survival (OS) and 5 year BCR (secondary aims). In this mono-institutional retrospective study, 549 Caucasian patients (a discovery set n = 418; a replication set n = 131) were affected by locally advanced PCa and homogeneously treated with RT. In the training set, associations were made between 447 SNPs in 77 genes of the immune system; and 10 year BCR and 10 year OS were tested through a multivariate Cox proportional hazard model. Significant SNPs (p-value < 0.05, q-value < 0.15) were analyzed in the replication set. Replicated SNPs were tested for 5 year BCR in both sets of patients. A polymorphism in the PDL1 gene (rs4143815) was the unique potential genetic variant of 10 year BCR (training set: p = 0.003, HR (95% CI) = 0.58 (0.41–0.83); replication set: p = 0.063, HR (95% CI) = 0.52 (0.26–1.04)) that was significantly associated with 5 year BCR (training set: p = 0.009, HR (95% CI) = 0.59 (0.40–0.88); replication set: p = 0.036, HR (95% CI) = 0.39 (0.16–0.94)). No biomarkers of OS were replicated. rs4143815-PDL1 arose as a new immunogenetic biomarker of BCR in PCa, giving new insights into the RT/immune system interaction, which could be potentially useful in new approaches using anti-PDL1 therapies for PCa. Full article
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Open AccessArticle
Reduced T-cell Numbers and Elevated Levels of Immunomodulatory Cytokines in Metastatic Prostate Cancer Patients De Novo Resistant to Abiraterone and/or Enzalutamide Therapy
Int. J. Mol. Sci. 2019, 20(8), 1831; https://doi.org/10.3390/ijms20081831
Received: 26 March 2019 / Revised: 10 April 2019 / Accepted: 11 April 2019 / Published: 13 April 2019
PDF Full-text (1580 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Currently, there are two Food and Drug Administration (FDA)-approved drugs for androgen deprivation therapy (ADT) of metastatic castration-resistant prostate cancer (mCRPC) patients: abiraterone and enzalutamide. However, our understanding of the effect of these therapies on the immune system in mCRPC patients remains limited. [...] Read more.
Currently, there are two Food and Drug Administration (FDA)-approved drugs for androgen deprivation therapy (ADT) of metastatic castration-resistant prostate cancer (mCRPC) patients: abiraterone and enzalutamide. However, our understanding of the effect of these therapies on the immune system in mCRPC patients remains limited. Here, we examined how abiraterone and enzalutamide treatment affects levels of soluble immune mediators in plasma and in circulating immune cells of 44 mCRPC patients. We found that the baseline levels of cytokines fibroblast growth factor (FGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 10 (IL-10), and IL-6 were significantly lower in ADT-sensitive compared to de novo resistant patients. In addition, resistant patients showed significantly lower T cell frequencies. When comparing the levels of cytokines over the course of treatment, we observed that the levels of proinflammatory mediators, such as interferon-γ (IFN-γ), IL-5, macrophage inflammatory protein 1 alpha (MIP-1α), and tumor necrosis factor alpha (TNFα), were significantly increased in the ADT-sensitive patients. At the same time, the abiraterone/enzalutamide therapy did not reduce the percentage of tolerogenic myeloid cell populations, such as polymorphonuclear myeloid-derived suppressor cells, which retained unaltered expression of programmed death-ligand 1 (PD-L1) and B7-H3. Overall, our results suggest that certain immune markers, such as IL-6 and the frequency of effector T cells, could be predictive of therapeutic response to ADT therapies in mCRPC patients. Full article
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Open AccessArticle
N-Linked Glycosylation and Near-Infrared Spectroscopy in the Diagnosis of Prostate Cancer
Int. J. Mol. Sci. 2019, 20(7), 1592; https://doi.org/10.3390/ijms20071592
Received: 25 February 2019 / Revised: 21 March 2019 / Accepted: 23 March 2019 / Published: 29 March 2019
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Abstract
Background: Performing a prostate biopsy is the most robust and reliable way to diagnose prostate cancer (PCa), and to determine the disease grading. As little to no biochemical markers for prostate tissue exist, we explored the possibilities of tissue N-glycosylation and near-infrared spectroscopy [...] Read more.
Background: Performing a prostate biopsy is the most robust and reliable way to diagnose prostate cancer (PCa), and to determine the disease grading. As little to no biochemical markers for prostate tissue exist, we explored the possibilities of tissue N-glycosylation and near-infrared spectroscopy (NIR) in PCa diagnosis. Methods: Tissue specimens from 100 patients (benign prostate hyperplasia (BPH), n = 50; and PCa, n = 50) were obtained. The fresh-frozen tissue was dispersed and a tissue N-glycosylation profile was determined. Consequently, the formalin-fixed paraffin-embedded slides were analyzed using NIR spectroscopy. A comparison was made between the benign and malignant tissue, and between the various Gleason scores. Results: A difference was observed for the tissue of N-glycosylation between the benign and malignant tissue. These differences were located in the fycosylation ratios and the total amount of bi- and tetra-antennary structures (all p < 0.0001). These differences were also present between various Gleason scores. In addition, the NIR spectra revealed changes between the benign and malignant tissue in several regions. Moreover, spectral ranges of 1055–1065 nm and 1450–1460 nm were significantly different between the Gleason scores (p = 0.0042 and p = 0.0195). Conclusions: We have demonstrated biochemical changes in the N-glycan profile of prostate tissue, which allows for the distinction between malignant and benign tissue, as well as between various Gleason scores. These changes can be correlated to the changes observed in the NIR spectra. This could possibly further improve the histological assessment of PCa diagnosis, although further method validation is needed. Full article
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Open AccessArticle
Gamma-Tocotrienol Induces Apoptosis in Prostate Cancer Cells by Targeting the Ang-1/Tie-2 Signalling Pathway
Int. J. Mol. Sci. 2019, 20(5), 1164; https://doi.org/10.3390/ijms20051164
Received: 29 January 2019 / Revised: 4 March 2019 / Accepted: 5 March 2019 / Published: 7 March 2019
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Abstract
Emerging evidence suggests that gamma-tocotrienol (γ-T3), a vitamin E isomer, has potent anti-cancer properties against a wide-range of cancers. γ-T3 not only inhibited the growth and survival of cancer cells in vitro, but also suppressed angiogenesis and tumour metastasis under in vivo conditions. [...] Read more.
Emerging evidence suggests that gamma-tocotrienol (γ-T3), a vitamin E isomer, has potent anti-cancer properties against a wide-range of cancers. γ-T3 not only inhibited the growth and survival of cancer cells in vitro, but also suppressed angiogenesis and tumour metastasis under in vivo conditions. Recently, γ-T3 was found to target cancer stem cells (CSCs), leading to suppression of tumour formation and chemosensitisation. Despite its promising anti-cancer potential, the exact mechanisms responsible for the effects of γ-T3 are still largely unknown. Here, we report the identification of Ang-1 (Angiopoietin-1)/Tie-2 as a novel γ-T3 downstream target. In prostate cancer cells, γ-T3 treatment leads to the suppression of Ang-1 at both the mRNA transcript and protein levels. Supplementing the cells with Ang-1 was found to protect them against the anti-CSC effect of γ-T3. Intriguingly, inactivation of Tie-2, a member receptor that mediates the effect of Ang-1, was found to significantly enhance the cytotoxic effect of γ-T3 through activation of AMP-activated protein kinase (AMPK) and subsequent interruption of autophagy. Our results highlighted the therapeutic potential of using γ-T3 in combination with a Tie-2 inhibitor to treat advanced prostate cancer. Full article
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Open AccessArticle
Development of a Transcriptional Amplification System Based on the PEG3 Promoter to Target Androgen Receptor-Positive and -Negative Prostate Cancer Cells
Int. J. Mol. Sci. 2019, 20(1), 216; https://doi.org/10.3390/ijms20010216
Received: 3 December 2018 / Revised: 21 December 2018 / Accepted: 31 December 2018 / Published: 8 January 2019
PDF Full-text (2679 KB) | HTML Full-text | XML Full-text
Abstract
Localized prostate cancer (PCa) is often curable, whereas metastatic disease treated by castration inevitably progresses toward castration-resistant PCa (CRPC). Most CRPC treatments target androgen receptor (AR) signaling. However, not all CRPC cells rely on AR activity for survival and proliferation. With advances in [...] Read more.
Localized prostate cancer (PCa) is often curable, whereas metastatic disease treated by castration inevitably progresses toward castration-resistant PCa (CRPC). Most CRPC treatments target androgen receptor (AR) signaling. However, not all CRPC cells rely on AR activity for survival and proliferation. With advances in immunotherapy and fluid biopsies for cancer management, expression systems specific for both AR-positive and -negative PCa are required for virus-based vaccines and cell imaging. To target both AR-responsive and non-responsive cells, we developed a three-step transcriptional amplification (3STA) system based on the progression elevated gene-3 (PEG3) promoter named PEG3AP1-3STA. Notably, we report on different genetic modifications that significantly improved PEG3 promoter’s strength in PCa cells. Adenoviruses incorporating PEG3 promoter with and without transcriptional amplification systems were generated. The potential of PEG3AP1-3STA to target PCa cells was then evaluated in vitro and in vivo in androgen-responsive and non-responsive PCa cell lines. PEG3AP1-3STA was shown to be active in all PCa cell lines and not regulated by androgens, and its activity was amplified 97-fold compared to that of a non-amplified promoter. The PEG3AP1-3STA system can thus be used to target advanced AR+ and AR− cells for imaging or immunovirotherapy in advanced PCa. Full article
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Review

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Open AccessReview
A Rich Array of Prostate Cancer Molecular Biomarkers: Opportunities and Challenges
Int. J. Mol. Sci. 2019, 20(8), 1813; https://doi.org/10.3390/ijms20081813
Received: 27 March 2019 / Revised: 8 April 2019 / Accepted: 9 April 2019 / Published: 12 April 2019
PDF Full-text (627 KB) | HTML Full-text | XML Full-text
Abstract
Prostate cancer is the most prevalent non-skin cancer in men and is the leading cause of cancer-related death. Early detection of prostate cancer is largely determined by a widely used prostate specific antigen (PSA) blood test and biopsy is performed for definitive diagnosis. [...] Read more.
Prostate cancer is the most prevalent non-skin cancer in men and is the leading cause of cancer-related death. Early detection of prostate cancer is largely determined by a widely used prostate specific antigen (PSA) blood test and biopsy is performed for definitive diagnosis. Prostate cancer is asymptomatic in the early stage of the disease, comprises of diverse clinico-pathologic and progression features, and is characterized by a large subset of the indolent cancer type. Therefore, it is critical to develop an individualized approach for early detection, disease stratification (indolent vs. aggressive), and prediction of treatment response for prostate cancer. There has been remarkable progress in prostate cancer biomarker discovery, largely through advancements in genomic technologies. A rich array of prostate cancer diagnostic and prognostic tests has emerged for serum (4K, phi), urine (Progensa, T2-ERG, ExoDx, SelectMDx), and tumor tissue (ConfirmMDx, Prolaris, Oncoytype DX, Decipher). The development of these assays has created new opportunities for improving prostate cancer diagnosis, prognosis, and treatment decisions. While opening exciting opportunities, these developments also pose unique challenges in terms of selecting and incorporating these assays into the continuum of prostate cancer patient care. Full article
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Open AccessReview
Prediction Medicine: Biomarkers, Risk Calculators and Magnetic Resonance Imaging as Risk Stratification Tools in Prostate Cancer Diagnosis
Int. J. Mol. Sci. 2019, 20(7), 1637; https://doi.org/10.3390/ijms20071637
Received: 1 March 2019 / Revised: 27 March 2019 / Accepted: 29 March 2019 / Published: 2 April 2019
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Abstract
This review discusses the most recent evidence for currently available risk stratification tools in the detection of clinically significant prostate cancer (csPCa), and evaluates diagnostic strategies that combine these tools. Novel blood biomarkers, such as the Prostate Health Index (PHI) and 4Kscore, show [...] Read more.
This review discusses the most recent evidence for currently available risk stratification tools in the detection of clinically significant prostate cancer (csPCa), and evaluates diagnostic strategies that combine these tools. Novel blood biomarkers, such as the Prostate Health Index (PHI) and 4Kscore, show similar ability to predict csPCa. Prostate cancer antigen 3 (PCA3) is a urinary biomarker that has inferior prediction of csPCa compared to PHI, but may be combined with other markers like TMPRSS2-ERG to improve its performance. Original risk calculators (RCs) have the advantage of incorporating easy to retrieve clinical variables and being freely accessible as a web tool/mobile application. RCs perform similarly well as most novel biomarkers. New promising risk models including novel (genetic) markers are the SelectMDx and Stockholm-3 model (S3M). Prostate magnetic resonance imaging (MRI) has evolved as an appealing tool in the diagnostic arsenal with even stratifying abilities, including in the initial biopsy setting. Merging biomarkers, RCs and MRI results in higher performances than their use as standalone tests. In the current era of prostate MRI, the way forward seems to be multivariable risk assessment based on blood and clinical parameters, potentially extended with information from urine samples, as a triaging test for the selection of candidates for MRI and biopsy. Full article
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Open AccessReview
Glycans as Biomarkers in Prostate Cancer
Int. J. Mol. Sci. 2019, 20(6), 1389; https://doi.org/10.3390/ijms20061389
Received: 21 February 2019 / Revised: 7 March 2019 / Accepted: 17 March 2019 / Published: 19 March 2019
PDF Full-text (2354 KB) | HTML Full-text | XML Full-text
Abstract
Prostate cancer is the most commonly diagnosed malignancy in men, claiming over 350,000 lives worldwide annually. Current diagnosis relies on prostate-specific antigen (PSA) testing, but this misses some aggressive tumours, and leads to the overtreatment of non-harmful disease. Hence, there is an urgent [...] Read more.
Prostate cancer is the most commonly diagnosed malignancy in men, claiming over 350,000 lives worldwide annually. Current diagnosis relies on prostate-specific antigen (PSA) testing, but this misses some aggressive tumours, and leads to the overtreatment of non-harmful disease. Hence, there is an urgent unmet clinical need to identify new diagnostic and prognostic biomarkers. As prostate cancer is a heterogeneous and multifocal disease, it is likely that multiple biomarkers will be needed to guide clinical decisions. Fluid-based biomarkers would be ideal, and attention is now turning to minimally invasive liquid biopsies, which enable the analysis of tumour components in patient blood or urine. Effective diagnostics using liquid biopsies will require a multifaceted approach, and a recent high-profile review discussed combining multiple analytes, including changes to the tumour transcriptome, epigenome, proteome, and metabolome. However, the concentration on genomics-based paramaters for analysing liquid biopsies is potentially missing a goldmine. Glycans have shown huge promise as disease biomarkers, and data suggests that integrating biomarkers across multi-omic platforms (including changes to the glycome) can improve the stratification of patients with prostate cancer. A wide range of alterations to glycans have been observed in prostate cancer, including changes to PSA glycosylation, increased sialylation and core fucosylation, increased O-GlcNacylation, the emergence of cryptic and branched N-glyans, and changes to galectins and proteoglycans. In this review, we discuss the huge potential to exploit glycans as diagnostic and prognostic biomarkers for prostate cancer, and argue that the inclusion of glycans in a multi-analyte liquid biopsy test for prostate cancer will help maximise clinical utility. Full article
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Open AccessReview
Focal Neuroendocrine Differentiation of Conventional Prostate Adenocarcinoma as a Prognostic Factor after Radical Prostatectomy: A Systematic Review and Meta-Analysis
Int. J. Mol. Sci. 2019, 20(6), 1374; https://doi.org/10.3390/ijms20061374
Received: 2 February 2019 / Revised: 11 March 2019 / Accepted: 13 March 2019 / Published: 19 March 2019
PDF Full-text (1194 KB) | HTML Full-text | XML Full-text
Abstract
The biologic and prognostic value of focal neuroendocrine differentiation (NED) in conventional prostate adenocarcinoma (PC) patients who undergo radical prostatectomy (RP) remains controversial. In this systematic review and meta-analysis, we assessed the association of focal NED in conventional PC with oncological outcomes after [...] Read more.
The biologic and prognostic value of focal neuroendocrine differentiation (NED) in conventional prostate adenocarcinoma (PC) patients who undergo radical prostatectomy (RP) remains controversial. In this systematic review and meta-analysis, we assessed the association of focal NED in conventional PC with oncological outcomes after RP. A literature search using PubMed, Scopus, Web of Science, and Cochrane Library was conducted on December 2018 to find relevant studies according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. We used a fixed-effect model to analyze the impact of focal NED in RP specimen on progression-free survival defined by biochemical recurrence (BCR). A total of 16 studies with the outcomes of disease progression and survival were eligible. No patient in these studies received androgen deprivation therapy prior to RP. Eleven studies found no significant correlation between focal NED and outcomes of interest, while five studies reported a significant association of focal NED assessed by immunohistochemical chromogranin A or serotonin staining with BCR or survival. Focal NED was associated with higher BCR rates after RP with a pooled HR of 1.39 (95% CI 1.07‒1.81) in five studies. No heterogeneity was reported in this analysis (I2 = 21.7%, p = 0.276). In conclusion, focal NED in conventional PC is associated with worse prognosis after RP. Its presence should be reported in pathologic reports and its true clinical impact should be assessed in well-designed prospective controlled studies. Full article
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Open AccessReview
Assessment of miR-98-5p, miR-152-3p, miR-326 and miR-4289 Expression as Biomarker for Prostate Cancer Diagnosis
Int. J. Mol. Sci. 2019, 20(5), 1154; https://doi.org/10.3390/ijms20051154
Received: 18 February 2019 / Accepted: 26 February 2019 / Published: 6 March 2019
PDF Full-text (986 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Prostate cancer (PCa) is one of the most commonly diagnosed cancers worldwide, accounting for almost 1 in 5 new cancer diagnoses in the US alone. The current non-invasive biomarker prostate specific antigen (PSA) has lately been presented with many limitations, such as low [...] Read more.
Prostate cancer (PCa) is one of the most commonly diagnosed cancers worldwide, accounting for almost 1 in 5 new cancer diagnoses in the US alone. The current non-invasive biomarker prostate specific antigen (PSA) has lately been presented with many limitations, such as low specificity and often associated with over-diagnosis. The dysregulation of miRNAs in cancer has been widely reported and it has often been shown to be specific, sensitive and stable, suggesting miRNAs could be a potential specific biomarker for the disease. Previously, we identified four miRNAs that are significantly upregulated in plasma from PCa patients when compared to healthy controls: miR-98-5p, miR-152-3p, miR-326 and miR-4289. This panel showed high specificity and sensitivity in detecting PCa (area under the curve (AUC) = 0.88). To investigate the specificity of these miRNAs as biomarkers for PCa, we undertook an in depth analysis on these miRNAs in cancer from the existing literature and data. Additionally, we explored their prognostic value found in the literature when available. Most studies showed these miRNAs are downregulated in cancer and this is often associated with cancer progression and poorer overall survival rate. These results suggest our four miRNA signatures could potentially become a specific PCa diagnostic tool of which prognostic potential should also be explored. Full article
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Open AccessReview
Jumping on the Bandwagon: A Review on the Versatile Applications of Gold Nanostructures in Prostate Cancer
Int. J. Mol. Sci. 2019, 20(4), 970; https://doi.org/10.3390/ijms20040970
Received: 4 February 2019 / Accepted: 21 February 2019 / Published: 23 February 2019
PDF Full-text (1566 KB) | HTML Full-text | XML Full-text
Abstract
Prostate cancer (PCa) has remarkably emerged as a prominent disease in the face of the male population. Conventional treatments like prostatectomy or radiation can be curative only if PCa is diagnosed at an early stage. In the field of targeted therapy, a bevy [...] Read more.
Prostate cancer (PCa) has remarkably emerged as a prominent disease in the face of the male population. Conventional treatments like prostatectomy or radiation can be curative only if PCa is diagnosed at an early stage. In the field of targeted therapy, a bevy of novel therapeutic approaches have left a landmark in PCa treatment and have proven to extend survival via distinct modes of actions. Nanotherapy has started to take root and has become the hype of the century by virtue of its abundant advantages. Scientists have invested a great deal of interest in the development of nanostructures such as gold nanoparticles (AuNPs), which hold particularly great hope for PCa theranostics. In this article, we present an overview of the studies published after 1998 that involve the use of different functionalized AuNPs to treat and diagnose PCa. Special reference is given to various in vitro and in vivo methods employed to shuttle AuNPs to PCa cells. Major studies show an enhancement of either detection or treatment of PCa when compared to their non-targeted counterparts, especially when AuNPs are tagged with specific ligands, such as antibodies, tea natural extracts, folate, anisamide, receptor inhibitors, and chitosan. Future approaches of treatment are dependent on those worthy multifunctional molecules, and are dictated by their ability to achieve a more versatile cancer therapeutic approach. Full article
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Tentative title: Precision medicine in prostate cancer: contribution of exosome characterization
Author: José Antonio López-Guerrero
Summary: Exosomes constitute a valuable source of biomarkers in many tumor types, including prostate cancer. The idea of the review would be to depict the state of the art of the potential use of these extracellular vesicles as a source of biomarkers and their potential use as diagnostic or prognostic tools in urine and serum from prostate cancer patients both in localized as in advanced disease.

Title: Jumping On The Bandwagon: A Review on the Versatile Applications of Gold Nanostructures in Prostate Cancer
Authors: Kamil Rahme, Monira Sarkis and Esther Ghanem
Abstract: Prostate cancer (PCa) has remarkably emerged as a prominent disease in the face of the male population. Conventional treatment like prostatectomy or radiation can be curative only if PCa is diagnosed at an early stage. In the field of targeted therapy, a bevy of novel therapeutic approaches have left a landmark in PCa treatment and have proven to extend survival via distinct mode of actions. Nanotherapy has started to take root and has become the hype of the century by virtue of its abundant advantages. Scientists have invested a great deal of interest in the development of gold nanoparticles (AuNPs), in particular, which holds great hope for PCa theranostics. In this article, we present an overview of the studies published after 1998, which involve the use of different functionalized gold nanostructures (Au NSs) to treat and diagnose PCa. Special reference is given to various in-vitro and in-vivo methods employed, to shuttle Au NSs to PCa cells. In the majority of the studies, an enhancement of either detection or treatment of PCa is observed when compared to their non-targeted counterparts. Adopting the use of polymer garnished Au NSs tagged with specific ligands such as antibodies, tea natural extracts, and receptor inhibitors, etc… lie at the heart of events necessary to effectively treat PCa. Future approaches of treatment are dependent on those worthy multifunctional nanoparticles and are dictated by their ability to achieve a more versatile cancer therapeutic approach.
Keywords: Gold nanoparticles; Bioconjugation; theranostics; prostate cancer; in vitro and in vivo studies.

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