scholarly journals A New Approach for Prostate Cancer Diagnosis by miRNA Profiling of Prostate-Derived Plasma Small Extracellular Vesicles

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2372
Author(s):  
Lidia Zabegina ◽  
Inga Nazarova ◽  
Nadezhda Nikiforova ◽  
Maria Slyusarenko ◽  
Elena Sidina ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Extracellular Vesicles ◽  
Click Reaction ◽  
Prostate Gland ◽  
Dna Aptamer ◽  
New Approach ◽  
Mirna Profiling ◽  
Healthy Donors ◽  
Diagnosis Method ◽  
Paramagnetic Beads

Vesicular miRNA has emerged as a promising marker for various types of cancer, including prostate cancer (PC). In the advanced stage of PC, the cancer-cell-derived small extracellular vesicles (SEVs) may constitute a significant portion of circulating vesicles and may mediate a detectable change in the plasma vesicular miRNA profile. However, SEVs secreted by small tumor in the prostate gland constitute a tiny fraction of circulating vesicles and cause undetectable miRNA pattern changes. Thus, the isolation and miRNA profiling of a specific prostate-derived fraction of SEVs can improve the diagnostic potency of the methods based on vesicular miRNA analysis. Prostate-specific membrane antigen (PSMA) was selected as a marker of prostate-derived SEVs. Super-paramagnetic beads (SPMBs) were functionalized by PSMA-binding DNA aptamer (PSMA–Apt) via a click reaction. The efficacy of SPMB–PSMA–Apt complex formation and PSMA(+)SEVs capture were assayed by flow cytometry. miRNA was isolated from the total population of SEVs and PSMA(+)SEVs of PC patients (n = 55) and healthy donors (n = 30). Four PC-related miRNAs (miR-145, miR-451a, miR-143, and miR-221) were assayed by RT-PCR. The click chemistry allowed fixing DNA aptamers onto the surface of SPMB with an efficacy of up to 89.9%. The developed method more effectively isolates PSMA(+)SEVs than relevant antibody-based technology. The analysis of PC-related miRNA in the fraction of PSMA(+)SEVs was more sensitive and revealed distinct diagnostic potency (AUC: miR-145, 0.76; miR-221, 0.7; miR-451a, 0.65; and miR-141, 0.64) than analysis of the total SEV population. Thus, isolation of prostate-specific SEVs followed by analysis of vesicular miRNA might be a promising PC diagnosis method.

scholarly journals Direct N-Glycosylation Profiling of Urine and Prostatic Fluid Glycoproteins and Extracellular Vesicles

2021 ◽  
Vol 9 ◽  
Author(s):  
Calvin R. K. Blaschke ◽  
Jordan P. Hartig ◽  
Grace Grimsley ◽  
Liping Liu ◽  
O. John Semmes ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Extracellular Vesicles ◽  
Prostate Gland ◽  
Imaging Mass Spectrometry ◽  
Clinical Samples ◽  
Timely Manner ◽  
Minimal Sample ◽  
Prostatic Fluid ◽  
Glycan Profiling ◽  
Cancer Tissues

Expressed prostatic secretions (EPS), also called post digital rectal exam urines, are proximal fluids of the prostate that are widely used for diagnostic and prognostic assays for prostate cancer. These fluids contain an abundant number of glycoproteins and extracellular vesicles secreted by the prostate gland, and the ability to detect changes in their N-glycans composition as a reflection of disease state represents potential new biomarker candidates. Methods to characterize these N-glycan constituents directly from clinical samples in a timely manner and with minimal sample processing requirements are not currently available. In this report, an approach is described to directly profile the N-glycan constituents of EPS urine samples, prostatic fluids and urine using imaging mass spectrometry for detection. An amine reactive slide is used to immobilize glycoproteins from a few microliters of spotted samples, followed by peptide N-glycosidase digestion. Over 100 N-glycan compositions can be detected with this method, and it works with urine, urine EPS, prostatic fluids, and urine EPS-derived extracellular vesicles. A comparison of the N-glycans detected from the fluids with tissue N-glycans from prostate cancer tissues was done, indicating a subset of N-glycans present in fluids derived from the gland lumens. The developed N-glycan profiling is amenable to analysis of larger clinical cohorts and adaptable to other biofluids.

scholarly journals Detection and Investigation of Extracellular Vesicles in Serum and Urine Supernatant of Prostate Cancer Patients

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 466
Author(s):  
Samanta Salvi ◽  
Erika Bandini ◽  
Silvia Carloni ◽  
Valentina Casadio ◽  
Michela Battistelli ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Extracellular Vesicles ◽  
Treatment Resistance ◽  
Cost Effective ◽  
Diagnostic Methods ◽  
Diagnostic Tools ◽  
Urological Cancers ◽  
Healthy Donors ◽  
Technical Issues ◽  
Biological Sources

Prostate Cancer (PCa) is one of the most frequently identified urological cancers. PCa patients are often over-diagnosed due to still not highly specific diagnostic methods. The need for more accurate diagnostic tools to prevent overestimated diagnosis and unnecessary treatment of patients with non-malignant conditions is clear, and new markers and methods are strongly desirable. Extracellular vesicles (EVs) hold great promises as liquid biopsy-based markers. Despite the biological and technical issues present in their detection and study, these particles can be found highly abundantly in the biofluid and encompass a wealth of macromolecules that have been reported to be related to many physiological and pathological processes, including cancer onset, metastasis spreading, and treatment resistance. The present study aims to perform a technical feasibility study to develop a new workflow for investigating EVs from several biological sources. Serum and urinary supernatant EVs of PCa, benign prostatic hyperplasia (BPH) patients, and healthy donors were isolated and investigated by a fast, easily performable, and cost-effective cytofluorimetric approach for a multiplex detection of 37 EV-antigens. We also observed significant alterations in serum and urinary supernatant EVs potentially related to BPH and PCa, suggesting a potential clinical application of this workflow.

scholarly journals Emerging Role of Extracellular Vesicles in Prostate Cancer

Endocrinology ◽  
2021 ◽  
Author(s):  
Megan Ludwig ◽  
Rhea Rajvansh ◽  
Justin M Drake
Keyword(s):  
Prostate Cancer ◽  
Extracellular Vesicles ◽  
Prostate Gland ◽  
The United States ◽  
Liquid Biopsies ◽  
Cellular Processes ◽  
Non Invasive ◽  
Common Cancer ◽  
Meaningful Communication

Abstract Prostate cancer (PCa) is the second most common cancer amongst men in the United States. While the use of PSA has improved the ability to screen and ultimately diagnose PCa, there still remains false positives due to non-cancerous conditions in the prostate gland itself and other prognostic biomarkers for PCa are needed. Contents within extracellular vesicles (EVs) have emerged as promising biomarkers that can give valuable information about disease state, and have the additional benefit of being acquired through non-invasive liquid biopsies. Meaningful communication between cancer cells and the microenvironment are carried by EVs, which impact important cellular processes in prostate cancer such as metastasis, immune regulation, and drug resistance.

scholarly journals Extracellular Vesicle Proteome in Prostate Cancer: A Comparative Analysis of Mass Spectrometry Studies

2021 ◽  
Vol 22 (24) ◽  
pp. 13605
Author(s):  
Rui Miguel Marques Bernardino ◽  
Ricardo Leão ◽  
Rui Henrique ◽  
Luis Campos Pinheiro ◽  
Prashant Kumar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Mass Spectrometry ◽  
Network Analysis ◽  
Extracellular Vesicles ◽  
Biomarker Discovery ◽  
Prostate Gland ◽  
Direct Interaction ◽  
Screening Methods ◽  
Proteomics Data ◽  
Discovery Research

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.

The correlation between lipid metabolism disorders and the prostate cancer

2020 ◽  
Vol 27 ◽  
Author(s):  
Justyna Dłubek ◽  
Jacek Rysz ◽  
Zbigniew Jabłonowski ◽  
Anna Gluba-Brzózka ◽  
Beata Franczyk
Keyword(s):  
Prostate Cancer ◽  
Fatty Acids ◽  
Lipid Metabolism ◽  
Cancer Progression ◽  
De Novo ◽  
Prostate Gland ◽  
Hdl Cholesterol ◽  
Atp Citrate Lyase ◽  
Male Population ◽  
Lipid Metabolism Disorders

: Prostate cancer is second most common cancer affecting male population all over the world. The existence of a correlation between lipid metabolism disorders and cancer of the prostate gland has been widely known for a long time. According to hypotheses, cholesterol may contribute to prostate cancer progression as a result of its participation as a signalling molecule in prostate growth and differentiation via numerous biologic mechanisms including Akt signalling and de novo steroidogenesis. The results of some studies suggest that increased cholesterol levels may be associated with higher risk of more aggressive course of disease. The aforementioned alterations in the synthesis of fatty acids are a unique feature of cancer and, therefore, it constitutes an attractive target for therapeutic intervention in the treatment of prostate cancer. Pharmacological or gene therapy aimed to reduce the activity of enzymes involved in de novo synthesis of fatty acids, FASN, ACLY (ATP citrate lyase) or SCD-1 (stearoyl-CoA desaturase) in particular, may result in cells growth arrest. Nevertheless, not all cancers are unequivocally associated with hypocholesterolaemia. It cannot be ruled out that the relationship between prostate cancer and lipid disorders is not a direct quantitative correlation between carcinogenesis and the amount of the circulating cholesterol. Perhaps the correspondence is more sophisticated and connected to the distribution of cholesterol fractions, or even sub-fractions of e.g. HDL cholesterol.

miRNA-expression in prostate cancer-associated fibroblasts and their extracellular vesicles

2021 ◽  
Vol 79 ◽  
pp. S584
Author(s):  
J. Linxweiler ◽  
H. Ayoubian ◽  
D. Himbert ◽  
M. Saar ◽  
M. Stöckle ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Extracellular Vesicles ◽  
Mirna Expression ◽  
Cancer Associated Fibroblasts

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 Detection of Prostate Cancer via IR Spectroscopic Analysis of Urinary Extracellular Vesicles: A Pilot Study

Membranes ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 591
Author(s):  
Xin-Le Yap ◽  
Bayden Wood ◽  
Teng-Aik Ong ◽  
Jasmine Lim ◽  
Bey-Hing Goh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Prostate Cancer Screening ◽  
Principal Component ◽  
Urine Samples ◽  
Cancer Type ◽  
Marker Proteins ◽  
Novel Strategy ◽  
Ir Spectroscopic

Extracellular vesicles (EVs) are membranous nanoparticles naturally released from living cells which can be found in all types of body fluids. Recent studies found that cancer cells secreted EVs containing the unique set of biomolecules, which give rise to a distinctive absorbance spectrum representing its cancer type. In this study, we aimed to detect the medium EVs (200–300 nm) from the urine of prostate cancer patients using Fourier transform infrared (FTIR) spectroscopy and determine their association with cancer progression. EVs extracted from 53 urine samples from patients suspected of prostate cancer were analyzed and their FTIR spectra were preprocessed for analysis. Characterization of morphology, particle size and marker proteins confirmed that EVs were successfully isolated from urine samples. Principal component analysis (PCA) of the EV’s spectra showed the model could discriminate prostate cancer with a sensitivity of 59% and a specificity of 81%. The area under curve (AUC) of FTIR PCA model for prostate cancer detection in the cases with 4–20 ng/mL PSA was 0.7, while the AUC for PSA alone was 0.437, suggesting the analysis of urinary EVs described in this study may offer a novel strategy for the development of a noninvasive additional test for prostate cancer screening.

scholarly journals Immunomagnetic sequential ultrafiltration (iSUF) platform for enrichment and purification of extracellular vesicles from biofluids

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jingjing Zhang ◽  
Luong T. H. Nguyen ◽  
Richard Hickey ◽  
Nicole Walters ◽  
Xinyu Wang ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Culture Media ◽  
Metastatic Breast ◽  
Clinical Samples ◽  
Clinical Use ◽  
Immunomagnetic Beads ◽  
Liquid Biopsies ◽  
Cell Culture Media ◽  
Non Invasive ◽  
Healthy Donors

AbstractExtracellular vesicles (EVs) derived from tumor cells have the potential to provide a much-needed source of non-invasive molecular biomarkers for liquid biopsies. However, current methods for EV isolation have limited specificity towards tumor-derived EVs that limit their clinical use. Here, we present an approach called immunomagnetic sequential ultrafiltration (iSUF) that consists of sequential stages of purification and enrichment of EVs in approximately 2 h. In iSUF, EVs present in different volumes of biofluids (0.5–100 mL) can be significantly enriched (up to 1000 times), with up to 99% removal of contaminating proteins (e.g., albumin). The EV recovery rate by iSUF for cell culture media (CCM), serum, and urine corresponded to 98.0% ± 3.6%, 96.0% ± 2.0% and 94.0% ± 1.9%, respectively (p > 0.05). The final step of iSUF enables the separation of tumor-specific EVs by incorporating immunomagnetic beads to target EV subpopulations. Serum from a cohort of clinical samples from metastatic breast cancer (BC) patients and healthy donors were processed by the iSUF platform and the isolated EVs from patients showed significantly higher expression levels of BC biomarkers (i.e., HER2, CD24, and miR21).

scholarly journals Molecular imaging of orthotopic prostate cancer with nanobubble ultrasound contrast agents targeted to PSMA

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu Wang ◽  
Al Christopher De Leon ◽  
Reshani Perera ◽  
Eric Abenojar ◽  
Ramamurthy Gopalakrishnan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Ultrasound Imaging ◽  
Prostate Gland ◽  
Ultrasound Contrast Agent ◽  
Tumor Model ◽  
Focal Therapy ◽  
Ultrasound Contrast Agents ◽  
Time Intensity Curve ◽  
Ultrasound Contrast

AbstractUltrasound imaging is routinely used to guide prostate biopsies, yet delineation of tumors within the prostate gland is extremely challenging, even with microbubble (MB) contrast. A more effective ultrasound protocol is needed that can effectively localize malignancies for targeted biopsy or aid in patient selection and treatment planning for organ-sparing focal therapy. This study focused on evaluating the application of a novel nanobubble ultrasound contrast agent targeted to the prostate specific membrane antigen (PSMA-targeted NBs) in ultrasound imaging of prostate cancer (PCa) in vivo using a clinically relevant orthotopic tumor model in nude mice. Our results demonstrated that PSMA-targeted NBs had increased extravasation and retention in PSMA-expressing orthotopic mouse tumors. These processes are reflected in significantly different time intensity curve (TIC) and several kinetic parameters for targeted versus non-targeted NBs or LUMASON MBs. These, may in turn, lead to improved image-based detection and diagnosis of PCa in the future.

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