scholarly journals Affinity Captured Urinary Extracellular Vesicles Provide mRNA and miRNA Biomarkers for Improved Accuracy of Prostate Cancer Detection: A Pilot Study

2020 ◽  
Vol 21 (21) ◽  
pp. 8330
Author(s):  
Michelle Davey ◽  
Sami Benzina ◽  
Marc Savoie ◽  
Guy Breault ◽  
Anirban Ghosh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Minimally Invasive ◽  
Extracellular Vesicles ◽  
Prostate Cancer Screening ◽  
Quantitative Polymerase Chain Reaction ◽  
Specific Antigen ◽  
Area Under The Curve ◽  
Test Accuracy ◽  
Expression Ratio ◽  
Tissue Biopsy

Serum prostate-specific antigen (sPSA) testing has helped to increase early detection of and decrease mortality from prostate cancer. However, since sPSA lacks specificity, an invasive prostate tissue biopsy is required to confirm cancer diagnosis. Using urinary extracellular vesicles (EVs) as a minimally invasive biomarker source, our goal was to develop a biomarker panel able to distinguish prostate cancer from benign conditions with high accuracy. We enrolled 56 patients in our study, 28 negative and 28 positive for cancer based on tissue biopsy results. Using our Vn96 peptide affinity method, we isolated EVs from post-digital rectal exam urines and used quantitative polymerase chain reaction to measure several mRNA and miRNA targets. We identified a panel of seven mRNA biomarkers whose expression ratio discriminated non-cancer from cancer with an area under the curve (AUC) of 0.825, sensitivity of 75% and specificity of 84%. We also identified two miRNAs whose combined score yielded an AUC of 0.744. A model pairing the seven mRNA and two miRNA panels yielded an AUC of 0.843, sensitivity of 79% and specificity of 89%. Addition of EV-derived PCA3 levels and clinical characteristics to the biomarker model further improved test accuracy. An AUC of 0.955, sensitivity of 86% and specificity of 93% were obtained. Hence, Vn96-isolated urinary EVs are a clinically applicable and minimally invasive source of mRNA and miRNA biomarkers with potential to improve on the accuracy of prostate cancer screening and diagnosis.

scholarly journals Profiling of Circulating microRNAs in Prostate Cancer Reveals Diagnostic Biomarker Potential

Diagnostics ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 188 ◽  
Author(s):  
Jacob Fredsøe ◽  
Anne K. I. Rasmussen ◽  
Peter Mouritzen ◽  
Marianne T. Bjerre ◽  
Peter Østergren ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Minimally Invasive ◽  
Specific Antigen ◽  
Transrectal Ultrasound ◽  
Digital Rectal Examination ◽  
Area Under The Curve ◽  
Diagnostic Tools ◽  
Test Set ◽  
Localized Disease ◽  
Clinically Significant

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.

scholarly journals Reducing Unnecessary Biopsy During Prostate Cancer Screening Using a Four-Kallikrein Panel: An Independent Replication

2010 ◽  
Vol 28 (15) ◽  
pp. 2493-2498 ◽  
Author(s):  
Andrew Vickers ◽  
Angel Cronin ◽  
Monique Roobol ◽  
Caroline Savage ◽  
Mari Peltola ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Cancer Screening ◽  
Randomized Study ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
Area Under The Curve ◽  
Population Based ◽  
Study Cohort ◽  
Low Grade ◽  
Total Psa

PurposeWe previously reported that a panel of four kallikrein forms in blood—total, free, and intact prostate-specific antigen (PSA) and kallikrein-related peptidase 2 (hK2)—can reduce unnecessary biopsy in previously unscreened men with elevated total PSA. We aimed to replicate our findings in a large, independent, representative, population-based cohort.Patients and MethodsThe study cohort included 2,914 previously unscreened men undergoing biopsy as a result of elevated PSA (≥ 3 ng/mL) in the European Randomized Study of Screening for Prostate Cancer, Rotterdam, with 807 prostate cancers (28%) detected. The cohort was randomly divided 1:3 into a training and validation set. Levels of kallikrein markers were compared with biopsy outcome.ResultsAddition of free PSA, intact PSA, and hK2 to a model containing total PSA and age improved the area under the curve from 0.64 to 0.76 and 0.70 to 0.78 for models without and with digital rectal examination results, respectively (P < .001 for both). Application of the panel to 1,000 men with elevated PSA would reduce the number of biopsies by 513 and miss 54 of 177 low-grade cancers and 12 of 100 high-grade cancers. Findings were robust to sensitivity analysis.ConclusionWe have replicated our previously published finding that a panel of four kallikreins can predict the result of biopsy for prostate cancer in men with elevated PSA. Use of this panel would dramatically reduce biopsy rates. A small number of men with cancer would be advised against immediate biopsy, but these men would have predominately low-stage, low-grade disease.

scholarly journals A Multivariate Diagnostic Model Based on Urinary EpCAM-CD9-Positive Extracellular Vesicles for Prostate Cancer Diagnosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Yibei Dai ◽  
Yiyun Wang ◽  
Ying Cao ◽  
Pan Yu ◽  
Lingyu Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Extracellular Vesicles ◽  
Diagnostic Performance ◽  
Specific Antigen ◽  
Transrectal Ultrasound ◽  
Area Under The Curve ◽  
Diagnostic Model ◽  
Model Based ◽  
Applied Machine Learning ◽  
Trus Biopsy

IntroductionProstate cancer (PCa) is one of the most frequently diagnosed cancers and the leading cause of cancer death in males worldwide. Although prostate-specific antigen (PSA) screening has considerably improved the detection of PCa, it has also led to a dramatic increase in overdiagnosing indolent disease due to its low specificity. This study aimed to develop and validate a multivariate diagnostic model based on the urinary epithelial cell adhesion molecule (EpCAM)-CD9–positive extracellular vesicles (EVs) (uEVEpCAM-CD9) to improve the diagnosis of PCa.MethodsWe investigated the performance of uEVEpCAM-CD9 from urine samples of 193 participants (112 PCa patients, 55 benign prostatic hyperplasia patients, and 26 healthy donors) to diagnose PCa using our laboratory-developed chemiluminescent immunoassay. We applied machine learning to training sets and subsequently evaluated the multivariate diagnostic model based on uEVEpCAM-CD9 in validation sets.ResultsResults showed that uEVEpCAM-CD9 was able to distinguish PCa from controls, and a significant decrease of uEVEpCAM-CD9 was observed after prostatectomy. We further used a training set (N = 116) and constructed an exclusive multivariate diagnostic model based on uEVEpCAM-CD9, PSA, and other clinical parameters, which showed an enhanced diagnostic sensitivity and specificity and performed excellently to diagnose PCa [area under the curve (AUC) = 0.952, P &lt; 0.0001]. When applied to a validation test (N = 77), the model achieved an AUC of 0.947 (P &lt; 0.0001). Moreover, this diagnostic model also exhibited a superior diagnostic performance (AUC = 0.917, P &lt; 0.0001) over PSA (AUC = 0.712, P = 0.0018) at the PSA gray zone.ConclusionsThe multivariate model based on uEVEpCAM-CD9 achieved a notable diagnostic performance to diagnose PCa. In the future, this model may potentially be used to better select patients for prostate transrectal ultrasound (TRUS) biopsy.

scholarly journals Prostate cancer screening: A survey of medical students’ knowledge in Lome, Togo, and associated determinants in a resource-limited African context

2021 ◽  
Vol 9 ◽  
pp. 205031212110328
Author(s):  
Tchin Darré ◽  
Toukilnan Djiwa ◽  
Tchilabalo Matchonna Kpatcha ◽  
Albadia Sidibé ◽  
Edoé Sewa ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Screening ◽  
Medical Students ◽  
Confidence Interval ◽  
Prostate Cancer Screening ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
P Value ◽  
Theoretical Knowledge ◽  
Practical Level

Objectives: The aims of this study were to assess the knowledge of medical students in Lomé about these means of screening for prostate cancer in a context of limited resources and controversy about prostate cancer screening, and to identify the determinants associated with these results. Methods: This was a prospective descriptive and cross-sectional study conducted in the form of a survey of medical students regularly enrolled at the Faculty of Health Sciences of the University of Lomé for the 2019–2020 academic years. Results: Of the 1635 eligible students, 1017 correctly completed the form, corresponding to a rate of 62.20%. The average age was 22 ± 3.35 years. The sex ratio (M/F) was 2.5. Undergraduate students were the most represented (53.69%). Students who had not received any training on prostate cancer were the most represented (57.13%). Only 12.88% of the students had completed a training course in urology. Concerning the prostate-specific antigen blood test, there was a statistically significant relationship between the students’ knowledge and some of their socio-demographic characteristics, namely age (p value = 0.0037; 95% confidence interval (0.50–1.77)); gender (p value = 0.0034; 95% confidence interval (1.43–2.38)); study cycle (p value ˂ 0.0001; 95% confidence interval (0.56–5.13)) and whether or not they had completed a placement in a urology department (p value ˂ 0.0001; 95% confidence interval (0.49–1.55)). On the contrary, there was no statistically significant relationship between students’ knowledge of the digital rectal examination and their study cycle (p value = 0.082; 95% confidence interval (0.18–3.44)). Conclusion: Medical students in Lomé have a good theoretical knowledge and a fair practical level of the digital rectal examination clinical examination and an average theoretical knowledge and a below average practical level of prostate-specific antigen, increasing however along the curriculum in the context of prostate cancer screening.

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.

Sign in / Sign up

Export Citation Format

Share Document