Urinary RNA-based biomarkers for prostate cancer detection (original) (raw)
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Urinary extracellular vesicles miRNA—A new era of prostate cancer biomarkers
Frontiers in Genetics
Prostate cancer is the second most common male cancer worldwide showing the highest rates of incidence in Western Europe. Although the measurement of serum prostate-specific antigen levels is the current gold standard in PCa diagnosis, PSA-based screening is not considered a reliable diagnosis and prognosis tool due to its lower sensitivity and poor predictive score which lead to a 22%–43% overdiagnosis, unnecessary biopsies, and over-treatment. These major limitations along with the heterogeneous nature of the disease have made PCa a very unappreciative subject for diagnostics, resulting in poor patient management; thus, it urges to identify and validate new reliable PCa biomarkers that can provide accurate information in regard to disease diagnosis and prognosis. Researchers have explored the analysis of microRNAs (miRNAs), messenger RNAs (mRNAs), small proteins, genomic rearrangements, and gene expression in body fluids and non-solid tissues in search of lesser invasive yet effic...
Urine Exosomes for Non-Invasive Assessment of Gene Expression and Mutations of Prostate Cancer
PloS one, 2016
The analysis of exosome/microvesicle (extracellular vesicles (EVs)) and the RNA packaged within them (exoRNA) has the potential to provide a non-invasive platform to detect and monitor disease related gene expression potentially in lieu of more invasive procedures such as biopsy. However, few studies have tested the diagnostic potential of EV analysis in humans. The ability of EV analysis to accurately reflect prostate tissue mRNA expression was examined by comparing urinary EV TMPRSS2:ERG exoRNA from pre-radical prostatectomy (RP) patients versus corresponding RP tissue in 21 patients. To examine the differential expression of TMPRSS2:ERG across patient groups a random urine sample was taken without prostate massage from a cohort of 207 men including prostate biopsy negative (Bx Neg, n = 39), prostate biopsy positive (Bx Pos, n = 47), post-radical prostatectomy (post-RP, n = 37), un-biopsied healthy age-matched men (No Bx, n = 44), and young male controls (Cont, n = 40). The use of...
Urinary-exosomal miR-2909: A novel pathognomonic trait of prostate cancer severity
The global occurrence of prostate cancer with a range of patient outcome has prompted various investigators to explore novel molecular biomarkers that can precisely detect and track this type of cancer severity. Several studies suggest that micro-RNAs have emerged to act as a new largely unexplored class of biomarkers because of their inherent stability, resilience and recruitment into exosomes present in various human body fluids. With this study, we aim to reveal the nature of urinary-exosomal miR-2909 & miR-615-3p recruitment in patients suffering from either prostate cancer (n = 90) or bladder cancer (n = 60) as compared to that in either prostate disease-control subjects having benign prostate hyperplasia (n = 10) or healthy subjects (n = 50). Unlike miR-615-3p, the urinary-exosomal miR-2909 recruitment was not only observed conspicuously in subjects having prostate cancer in comparison to bladder cancer but also the extent of urinary exosomal miR-2909 recruitment showed characteristic variation as a function of prostate cancer aggressiveness as compared to that of either urinary-exosomal miR-615-3p level or existing widely recognised serum prostate specifics antigen (PSA) biomarker of this cancer. In summary, we propose that the extent of urinary exosomal miR-2909 recruitment may provide a potential non-invasive candidate diagnostic marker for the detection of prostate cancer and its aggressiveness.
Long Non-Coding RNAs in Plasma and Urine as Potential Biomarkers in Prostate Cancer
Timisoara Medical Journal, 2021
(1) Introduction: Prostate cancer is the second leading cause of cancer-related death in men in developed countries. Due to the existing biomarkers' limitations, there is a stringent need to develop novel, better non-invasive markers for prostate cancer diagnostic and monitoring. (2) Material and methods: We assessed, by real-time PCR, the expression level of 84 long non-coding RNA (lncRNA) in plasma and the exosomes isolated from prostate cancer patients' plasma and urine. (3) Results: Only a few lncRNAs were detected in high abundance (Ct between 25 and 30 cycles) across all sample types, the vast majority showing relatively modest levels (Ct > 30 cycles). As expected, plasma and plasma exosomes contain far more lncRNA species than urine, irrespective of whether they originate from patients or controls. We identified two statistically significant dysregulated lncRNAs in prostate cancer samples vs. controls: RBM5-AS1, 2.89 times downregulated in plasma (p = 0.036), and SNHG16, 13.69 times upregulated (p = 0.029) in urine exosomes. (4) Conclusions: These preliminary data need further validation in additional independent, more extensive studies before they can be considered as biomarkers for prostate cancer.
Semen miRNAs Contained in Exosomes as Non-Invasive Biomarkers for Prostate Cancer Diagnosis
Scientific Reports
Although it is specific for prostatic tissue, serum prostate-specific antigen (PSA) screening has resulted in an over-diagnosis of prostate cancer (PCa) and many unnecessary biopsies of benign disease due to a well-documented low cancer specificity, thus improvement is required. We profiled the expression level of miRNAs contained in semen exosomes from men with moderately increased PSA levels to assess their usefulness, either alone or in addition to PSA marker, as non-invasive biomarkers, for the early efficient diagnosis and prognosis of PCa. An altered miRNA expression pattern was found by a high throughput profiling analysis in PCa when compared with healthy individuals (HCt) exosomal semen samples. The presence of vasectomy was taken into account for the interpretation of results. Fourteen miRNAs were selected for miRNA validation as PCa biomarkers in a subsequent set of semen samples. In this explorative study, we describe miRNA-based models, which included miRNA expression v...
Cancers
There is a clinical need to improve assessment of biopsy-naïve patients for the presence of clinically significant prostate cancer (PCa). In this study, we investigated whether the robust integration of expression data from urinary extracellular vesicle RNA (EV-RNA) with urine proteomic metabolites can accurately predict PCa biopsy outcome. Urine samples collected within the Movember GAP1 Urine Biomarker study (n = 192) were analysed by both mass spectrometry-based urine-proteomics and NanoString gene-expression analysis (167 gene-probes). Cross-validated LASSO penalised regression and Random Forests identified a combination of clinical and urinary biomarkers for predictive modelling of significant disease (Gleason Score (Gs) ≥ 3 + 4). Four predictive models were developed: ‘MassSpec’ (CE-MS proteomics), ‘EV-RNA’, and ‘SoC’ (standard of care) clinical data models, alongside a fully integrated omics-model, deemed ‘ExoSpec’. ExoSpec (incorporating four gene transcripts, six peptides, ...
A Multiplex Assay to Measure RNA Transcripts of Prostate Cancer in Urine
PLoS ONE, 2012
The serum prostate-specific antigen (PSA) test has a high false positive rate. As a single marker, PSA provides limited diagnostic information. A multi-marker test capable of detecting not only tumors but also the potentially lethal ones provides an unmet clinical need. Using the nanoString nCounter gene expression system, a 20-gene multiplex test was developed based on digital gene counting of RNA transcripts in urine as a means to detect prostate cancer. In this test, voided urine is centrifuged to pellet cells and the purified RNA is amplified for hybridization to preselected probesets. Amplification of test cell line RNA appeared not to introduce significant bias, and the counts matched well with gene abundance levels as measured by DNA microarrays. For data analysis, the individual counts were compared to that of b2 microglobulin, a housekeeping gene. Urine samples of 5 pre-operative cases and 2 non-cancer were analyzed. Pathology information was then retrieved. Signals for a majority of the genes were low for non-cancer and low Gleason scores, and 6/6 known prostate cancer markers were positive in the cases. One case of Gleason 4+5 showed, in contrast, strong signals for all cancer-associated markers, including CD24. One non-cancer also showed signals for all 6 cancer markers, and this man might harbor an undiagnosed cancer. This multiplex test assaying a natural waste product can potentially be used for screening, early cancer detection and patient stratification. Diagnostic information is gained from the RNA signatures that are associated with cell types of prostate tumors.
Molecular cancer, 2017
The aim of this study was to identify microRNAs in urinary exosomes that are differently expressed in prostate cancer patients and healthy donors. For this purpose, RNA was extracted from urinary exosomes from 20 prostate cancer patients and 9 healthy males and the microRNAs were analyzed by next generation sequencing. Interestingly, 5 microRNAs - miR-196a-5p, miR-34a-5p, miR-143-3p, miR-501-3p and miR-92a-1-5p - were significantly downregulated in exosomes from prostate cancer patients. Furthermore, RT-qPCR analysis of an independent cohort of 28 prostate cancer patients and 19 healthy males confirmed that miR-196a-5p and miR-501-3p were downregulated in prostate cancer samples. These results suggest that specific microRNAs in urinary exosomes might serve as non-invasive biomarkers for prostate cancer. In particular, miR-196a-5p and miR-501-3p are promising biomarkers that need to be further studied in large patient cohorts.
International Journal of Molecular Sciences, 2020
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 yie...