scholarly journals Biomarkers in Prostate Cancer Diagnosis: From Current Knowledge to the Role of Metabolomics and Exosomes

2021 ◽  
Vol 22 (9) ◽  
pp. 4367
Author(s):  
Stefano Salciccia ◽  
Anna Laura Capriotti ◽  
Aldo Laganà ◽  
Stefano Fais ◽  
Mariantonia Logozzi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Mammalian Cells ◽  
Current Knowledge ◽  
Prostate Gland ◽  
Specific Antigen ◽  
Metabolic Phenotype ◽  
Technical Equipment ◽  
Level Of Evidence ◽  
Genomics And Proteomics ◽  
High Level

Early detection of prostate cancer (PC) is largely carried out using assessment of prostate-specific antigen (PSA) level; yet it cannot reliably discriminate between benign pathologies and clinically significant forms of PC. To overcome the current limitations of PSA, new urinary and serum biomarkers have been developed in recent years. Although several biomarkers have been explored in various scenarios and patient settings, to date, specific guidelines with a high level of evidence on the use of these markers are lacking. Recent advances in metabolomic, genomics, and proteomics have made new potential biomarkers available. A number of studies focused on the characterization of the specific PC metabolic phenotype using different experimental approaches has been recently reported; yet, to date, research on metabolomic application for PC has focused on a small group of metabolites that have been known to be related to the prostate gland. Exosomes are extracellular vesicles that are secreted from all mammalian cells and virtually detected in all bio-fluids, thus allowing their use as tumor biomarkers. Thanks to a general improvement of the technical equipment to analyze exosomes, we are able to obtain reliable quantitative and qualitative information useful for clinical application. Although some pilot clinical investigations have proposed potential PC biomarkers, data are still preliminary and non-conclusive.

scholarly journals Prostate Cancer Liquid Biopsy Biomarkers’ Clinical Utility in Diagnosis and Prognosis

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3373
Author(s):  
Milena Matuszczak ◽  
Jack A. Schalken ◽  
Maciej Salagierski
Keyword(s):  
Prostate Cancer ◽  
Liquid Biopsy ◽  
Current Knowledge ◽  
Prostate Gland ◽  
Specific Antigen ◽  
Transrectal Ultrasound ◽  
Digital Rectal Examination ◽  
Cost Effective ◽  
Non Invasive ◽  
Diagnosis And Prognosis

Prostate cancer (PCa) is the most common cancer in men worldwide. The current gold standard for diagnosing PCa relies on a transrectal ultrasound-guided systematic core needle biopsy indicated after detection changes in a digital rectal examination (DRE) and elevated prostate-specific antigen (PSA) level in the blood serum. PSA is a marker produced by prostate cells, not just cancer cells. Therefore, an elevated PSA level may be associated with other symptoms such as benign prostatic hyperplasia or inflammation of the prostate gland. Due to this marker’s low specificity, a common problem is overdiagnosis, which leads to unnecessary biopsies and overtreatment. This is associated with various treatment complications (such as bleeding or infection) and generates unnecessary costs. Therefore, there is no doubt that the improvement of the current procedure by applying effective, sensitive and specific markers is an urgent need. Several non-invasive, cost-effective, high-accuracy liquid biopsy diagnostic biomarkers such as Progensa PCA3, MyProstateScore ExoDx, SelectMDx, PHI, 4K, Stockholm3 and ConfirmMDx have been developed in recent years. This article compares current knowledge about them and their potential application in clinical practice.

scholarly journals The role of the androgen receptor as a driver and mitigator of cellular stress

2020 ◽  
Vol 65 (2) ◽  
pp. R19-R33
Author(s):  
Dimitrios Doultsinos ◽  
Ian Mills
Keyword(s):  
Prostate Cancer ◽  
Protein Synthesis ◽  
Androgen Receptor ◽  
Cancer Progression ◽  
Prostate Gland ◽  
Specific Antigen ◽  
Nuclear Hormone Receptor ◽  
Biological Processes ◽  
Normal Prostate ◽  
Mtor Activity

Prostate cancer is a high-incidence male cancer, which is dependent on the activity of a nuclear hormone receptor, the androgen receptor (AR). Since the AR is required for both normal prostate gland development and for prostate cancer progression, it is possible that prostate cancer evolves from perturbations in AR-dependent biological processes that sustain specialist glandular functions. The archetypal example of course is the use of prostate specific antigen (PSA), an organ-type specific component of the normal prostate secretome, as a biomarker of prostate cancer. Furthermore, localised prostate cancer is characterised by a low proliferative index and a heterogenous array of somatic mutations aligned to a multifocal disease pattern. We and others have identified a number of biological processes that are AR dependent and represent aberrations in significant glandular processes. Glands are characterised by high rates of metabolic activity including protein synthesis supported by co-dependent processes such as glycosylation, organelle biogenesis and vesicle trafficking. Impairments in anabolic metabolism and in protein folding/processing will inevitably impose proteotoxic and oxidative stress on glandular cells and, in particular, luminal epithelial cells for which secretion is their primary function. As cancer develops there is also significant metabolic dysregulation including impaired negative feedback effects on glycolytic and anabolic activity under conditions of hypoxia and heightened protein synthesis due to dysregulated PI 3-kinase/mTOR activity. In this review we will focus on the components of the AR regulome that support cancer development as well as glandular functions focussing on the unfolded protein response and on regulators of mTOR activity.

Cancer screening and prevention in gynaecology

2020 ◽  
pp. 755-765
Author(s):  
Lynette Denny ◽  
Rengaswamy Sankaranarayan
Keyword(s):  
Specific Antigen ◽  
Careful Consideration ◽  
World Health ◽  
Clear Understanding ◽  
Level Of Evidence ◽  
Access To Health ◽  
Screening And Prevention ◽  
Health Organization ◽  
High Level ◽  
Current Screening

In 1968, the World Health Organization published guidelines on the principles and practice of screening for disease, which are often referred to as the ‘Wilson and Jungner criteria’. These principles are still applicable today. With the onset of genetic screening, new controversies around screening emerged and in 2008, Andermann et al. synthesized and modified the Wilson criteria. Screening is a systematic attempt to select those who are at high risk of a specific disease from among apparently healthy individuals. The ultimate aim of screening is prevention of disease or to detect disease at an early, curable stage. There are many controversies about screening for cancer, such as the use of prostatic-specific antigen screening for prostate cancer, mammography screening for breast cancer, and debates around current screening for colorectal, lung, and cervical cancers. Controversies also exist with regard to the level of evidence required before screening for a disease is initiated. Even if there is a high level of evidence for efficacy and effectiveness, how the programme should be implemented needs careful consideration, particularly a clear understanding of benefits versus harms, potential or actual. In some countries, mass population screening programmes are implemented and in others, screening is dependent on access to health insurance. This chapter explores past and current screening activities among women for early detection and prevention of gynaecological cancers including cervical, ovarian, and endometrial cancers and discusses screening for vulval and vaginal cancer.

The decision of targeted, systematic or combined biopsy in a biopsy naïve patient for the diagnosis of prostate cancer, can be made on the basis of multiparametric magnetic resonance imaging

2019 ◽  
Vol 13 (3) ◽  
pp. 198-204
Author(s):  
Debashis Sarkar ◽  
Debashis Nandi ◽  
Sameer Gangoli ◽  
James Hicks ◽  
Paul Carter
Keyword(s):  
Magnetic Resonance Imaging ◽  
Prostate Cancer ◽  
Magnetic Resonance ◽  
Current Trend ◽  
Specific Antigen ◽  
Cost Effective ◽  
Resonance Imaging ◽  
Level Of Evidence ◽  
Naive Patient ◽  
Multiparametric Magnetic Resonance Imaging

Introduction: The current trend to implement multiparametric magnetic resonance imaging (mpMRI)-guided targeted biopsy (TB) as primary biopsy for the diagnosis of suspected prostate cancer and to avoid systematic biopsy (SB) is growing. However, concern remains regarding missing clinically significant (Cs) cancer on the normal mpMRI areas of the prostate. Therefore, we compared the normal and abnormal areas from mpMRI at the same prostate biopsy, using simultaneous SB and TB technique. Methods: A prospective, comparative effectiveness study included 134 patients initially referred for primary biopsy (from October 2017 to June 2018); 100 men were selected, mean age 68 years, with a median level of prostate specific antigen of 7.6, with average prostate volume of 52 cm3 (T3 disease and prostate imaging reporting and data system (PI-RADS) score < 3 were excluded). All underwent six cores TB (median), from an average of two lesions on mpMRI and also eight cores SB (median) from normal mpMRI areas of the prostate after informed consent. Results: The combined (SB + TB) biopsy cancer detection rate was 67%, 51% having Cs disease. For Cs cancer, 35 patients were detected by both techniques. TB missed four Cs cancer (95% confidence interval (CI), p < 0.0001). Fewer men in the TB group than in the SB group were found to have clinically insignificant (Ci) cancer (95% CI, p < 0.0001). No Cs cancer diagnosis was missed on TB from PI-RADS 5 lesion. Overall, 4% Cs cancers were missed on TB and avoided over diagnosis of 9% Ci cancer. Conclusions: Cognitive TB didn’t miss any Cs cancer from PI-RADS 5 lesion found on mpMRI. Only doing Cognitive TB on PI-RADS 5 lesion would save time, reduce workload and will be cost effective both for Urology and Pathology. PI-RADS 3 and 4 lesions on mpMRI will benefit from adding systematic samples. Level of evidence: 4 Oxford Centre for Evidence-Based Medicine (CEBM).

scholarly journals Role of miRNALet-7and Its Major Targets in Prostate Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Siegfried Wagner ◽  
Anaclet Ngezahayo ◽  
Hugo Murua Escobar ◽  
Ingo Nolte
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Target Genes ◽  
Prostate Cancer Screening ◽  
Prostate Gland ◽  
Specific Antigen ◽  
Current Treatment ◽  
Diagnostic Potential ◽  
Major Interest ◽  
Hormone Refractory

Prostate cancer is worldwide the sixth leading cause of cancer related death in men thus early detection and successful treatment are still of major interest. The commonly performed screening of the prostate-specific antigen (PSA) is controversially discussed, as in many patients the prostate-specific antigen levels are chronically elevated in the absence of cancer. Due to the unsatisfying efficiency of available prostate cancer screening markers and the current treatment outcome of the aggressive hormone refractory prostate cancer, the evaluation of novel molecular markers and targets is considered an issue of high importance. MicroRNAs are relatively stable in body fluids orchestrating simultaneously the expression of many genes. These molecules are currently discussed to bear a greater diagnostic potential than protein-coding genes, being additionally promising therapeutic drugs and/or targets. Herein we review the potential impact of the microRNAlet-7family on prostate cancer and show how deregulation of several of its target genes could influence the cellular equilibrium in the prostate gland, promoting cancer development as they do in a variety of other human malignant neoplasias.

miRNAs as novel biomarkers in the management of prostate cancer

2017 ◽  
Vol 55 (5) ◽  
Author(s):  
Xavier Filella ◽  
Laura Foj
Keyword(s):  
Prostate Cancer ◽  
Current Knowledge ◽  
Expression Patterns ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
New Approach ◽  
Novel Biomarkers ◽  
Non Coding Rnas ◽  
Underlying Mechanisms ◽  
New Biomarkers

AbstractmicroRNAs (miRNAs) are small non-coding RNAs that control gene expression posttranscriptionally and are part of the giant non codifying genoma. Cumulating data suggest that miRNAs are promising potential biomarkers for many diseases, including cancer. Prostate cancer (PCa) detection is currently based in the serum prostate-specific antigen biomarker and digital rectal examination. However, these methods are limited by a low predictive value and the adverse consequences associated with overdiagnosis and overtreatment. New biomarkers that could be used for PCa detection and prognosis are still needed. Recent studies have demonstrated that aberrant expressions of microRNAs are associated with the underlying mechanisms of PCa. This review attempts to extensively summarize the current knowledge of miRNA expression patterns, as well as their targets and involvement in PCa pathogenesis. We focused our review in the value of circulating and urine miRNAs as biomarkers in PCa patients, highlighting the existing discrepancies between different studies, probably associated with the important methodological issues related to their quantitation and normalization. The majority of studies have been performed in serum or plasma, but urine obtained after prostate massage appears as a new way to explore the usefulness of miRNAs. Large screening studies to select a miRNA profile have been completed, but bioinformatics tools appear as a new approach to select miRNAs that are relevant in PCa development. Promising preliminary results were published concerning miR-141, miR-375 and miR-21, but larger and prospective studies using standardized methodology are necessary to define the value of miRNAs in the detection and prognosis of PCa.

scholarly journals PREPARASI PEREAKSI KIT IMMUNORADIOMETRlCASSAY FREE PROSTATE SPECIFIC ANTIGEN UNTUK DETEKSI KANKER PROSTAT

2013 ◽  
Vol 15 (2) ◽  
pp. 14-24
Author(s):  
Puji Widayati ◽  
Gina Mondrida ◽  
Sri Setiyowati ◽  
Agus Ariyanto ◽  
V. Yulianti Susilo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Prostate Gland ◽  
Specific Antigen ◽  
Prostatic Hyperplasia ◽  
Free Condition ◽  
Free Psa ◽  
Prostate Enlargement ◽  
Assay Design ◽  
Benign Prostate

Prostate Specific Antigen (PSA) is a glycoprotein with a molecular weight of approximately 34,000 daltons serine protease secreted exclusively by prostatic epithelial cells that lining acini and prostate gland. Increased of PSA levels can be caused by prostate cancer or benign prostate enlargement (benign prostatic hyperplasia, BPH). PSA in the blood was found in the free condition (free PSA) and most of the bound protein (complexed-PSA, c-PSA). Measuring levels of PSA was found in the blood can be done by several methods such as by immunoradiometricassay (IRMA) methods or ELISA methods. IRMA method is one of immunoassay techniques using radionuclides ,/' 125 oJ I as a tracer, so the sample in small 13 quantity can be detected The purpose of this study was obtained PSA reagent kit that includes 1251labeled PSA as a tracer, PSA coated tube and PSA standard that requirements of the kit, then it can be optimized assay design, that eventually PSA reagent kit can be used for early detection of prostate cancer. It has been done labeling of Mab PSA using 125 1with reaction time was 90 seconds, amount of PSA MAb was 75 ugram and the activity of Na_ 125I was 1000 flCi. Preaparation of PSA coated tube using 0.05 M Na2C03 solution, at pH: 9.6 with volume was 250 ml., standard PSA with 0.025 Mphosphate buffer at pH 7.4 containing 5% BSA and 0.1% NaN3, and resulting at 1,25% and 14,12% respectively of NSB and BIT that requirement of the kit.Keywords: Prostate cancer, PSA, IRMA,NSB, Maximum Binding

Novel Diagnostic Biomarkers of Prostate Cancer: An Update

2019 ◽  
Vol 26 (6) ◽  
pp. 1045-1058 ◽  
Author(s):  
Umberto Anceschi ◽  
Gabriele Tuderti ◽  
Franco Lugnani ◽  
Pier Mario Biava ◽  
Gianni Malossini ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
English Language ◽  
Treatment Effectiveness ◽  
Current Knowledge ◽  
Specific Antigen ◽  
Diagnostic Biomarkers ◽  
Molecular Features ◽  
Prostate Health Index ◽  
Meta Analyses ◽  
Prostate Health

Objective:In recent years, several biomarkers alternative to standard prostate specific antigen (PSA) for prostate cancer (PCa) diagnosis have become available. The aim of this systematic review is to assess the current knowledge about alternative serum and urinary biomarkers for the diagnosis of PCa.Material and Methods:A research was conducted in Medline, restricted to English language articles published between December 2014 and June 2018 with the aim to update previously published series on PCa biomarkers. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) criteria were used for selecting studies with the lowest risk of bias.Results:Emerging role and actual controversies on serum and urine alternative biomarkers to standard PSA for PCa diagnosis, staging and prognosis assessment, such as prostate health index (PHI), PCA3, ConfirmMDx, Aberrant PSA glycosylation, MiPS, miRNAs are critically presented in the current review.Conclusion:Although the use of several biomarkers has been recommended or questioned by different international guidelines, larger prospective randomized studies are still necessary to validate their efficacy in PCa detection, discrimination, prognosis and treatment effectiveness. To date, only PHI and 4Kscore have shown clinical relevance for discriminating more aggressive PCa. Furthermore, a new grading classification based on molecular features relevant for PCa risk-stratification and tailoring treatment is still needed.

Application of gene transfer technologies to the production of enzyme reference materials: example of gamma-glutamyltransferase

1993 ◽  
Vol 39 (8) ◽  
pp. 1573-1589 ◽  
Author(s):  
G Siest ◽  
T Oster ◽  
A Visvikis ◽  
C Thioudellet ◽  
C Angèle ◽  
...  
Keyword(s):  
Recombinant Proteins ◽  
Reference Materials ◽  
Mammalian Cells ◽  
Current Knowledge ◽  
Clinical Chemistry ◽  
Expression System ◽  
Experimental Conditions ◽  
Gamma Glutamyltransferase ◽  
Native Proteins ◽  
High Level

Abstract Protein reference materials are traditionally prepared by purification from mammalian or human tissues. The supply of these tissues is limited; consequently, there is a growing need for applied molecular and cellular biology technologies for the production of human recombinant proteins. This is especially true when only small amounts of the proteins are available in the tissues. We review the current knowledge necessary for high-level production of such proteins in different heterologous expression systems, using our data on gamma-glutamyltransferase (EC 2.3.2.2) as an example. We describe the steps required to achieve the expression of enzymes and other proteins in Escherichia coli, yeast, or mammalian cells. We list many of the problems investigators may face in preparing recombinant proteins, and provide information on selecting the most appropriate system as well as the most favorable experimental conditions. Depending on the expression system, recombinant proteins can potentially be obtained for most, if not all, enzymes of interest in clinical chemistry, and such proteins should possess characteristics very similar to those of the corresponding human native proteins. Studies suggest that these products can be used as reference materials in clinical chemistry laboratories.

A single centre service evaluation of the pre-biopsy mpMRI pathway for prostate cancer diagnosis

2022 ◽  
pp. 205141582110659
Author(s):  
Mark Kong ◽  
Louise Lee ◽  
Kevin Mulcahy ◽  
Arumugam Rajesh
Keyword(s):  
Prostate Cancer ◽  
Cancer Diagnosis ◽  
Waiting Times ◽  
Specific Antigen ◽  
Service Evaluation ◽  
Level Of Evidence ◽  
Prostate Cancer Diagnosis ◽  
Psa Density ◽  
Tertiary Centre ◽  
Clinically Significant

Aim: To study the efficacy and impact of the local pre-biopsy multiparametric magnetic resonance imaging (mpMRI) pathway for prostate cancer diagnosis. Methods: In this tertiary centre, 570 patients had prostate mpMRI across a 6-month period in 2019. A total of 511 patients met inclusion criteria for retrospective analysis. MRI reporting used the Prostate Imaging-Reporting and Data System (PI-RADS) v2.1. These were assessed alongside histological outcomes and diagnostic times. PI-RADS ⩾ 3 were recommended for biopsy consideration. Gleason scoring ⩾ 3 + 4 and 3 + 3 were used to define clinically and non-clinically significant prostate cancer (csPCa and nsPCa), respectively. Results: Overall prostate cancer prevalence was 40% (204/511, csPCa in 31.1%) with an overall biopsy avoidance of 32.1% (164/511). Around 69.7% (356/511) scored PI-RADS ⩾ 3 and 30.3% (155/511) scored PI-RADS 1–2. About 22.6% (35/155) of PI-RADS 1–2 patients proceeded to biopsy, demonstrating a negative predictive value of 91.43% for csPCa. For PI-RADS ⩾ 3 patients, 63.4% (197/312) of those biopsied had cancer (Gleason ⩾ 3 + 3), with 50% (156/312) demonstrating csPCa. Around 76.7% (102/133) of PI-RADS 5, 35.3% (48/136) of PI-RADS 4, 14.0% (6/43) of PI-RADS 3 and 8.6% (3/35) of PI-RADS 1–2 scores demonstrated csPCa. Overall median prostate-specific antigen (PSA) density was 0.15 ng/mL2 (IQR: 0.10–0.27/mL2). PSA density were significantly different across PI-RADS cohorts ( H = 118.8, p < 0.0001) and across all three biopsy outcomes ( H = 99.72, p < 0.0001). Only 34.3% (119/347) of biopsied patients met the NHS 28-day standard. MRI acquisition and reporting met the 14-day local standard in 96.1% (491/511). The biopsy was the most delayed component with a median of 20 days (IQR: 8–43). Conclusion: Pre-biopsy mpMRI with PI-RADS scoring safely avoided biopsy in almost one-third (32.1%) of patients. The use of PSA-density in risk stratifying PI-RADS 3 lesions has informed local practice in the period 2020–2021, with implementation of a PSA-density threshold of 0.12 ng/mL2. Biopsy scheduling issues and anaesthetic requirements need to be overcome to improve diagnostic waiting times. Level of evidence: 2

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