Biomarker screening for the early detection of prostate cancer using an exosomal-enrichment RNA liquid biopsy test.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15553-e15553
Author(s):  
Douglas Roberts ◽  
Emily Mitsock ◽  
Olubode Ogunlusi ◽  
Seth Yu ◽  
Johan Skog
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
High Risk ◽  
Early Detection ◽  
Nucleic Acids ◽  
Prostate Gland ◽  
Grey Zone ◽  
Psa Test ◽  
Non Invasive ◽  
Urine Exosomes

e15553 Background: Prostate cancer is one of the most common cancers in men, with approximately 10% of all new cancer cases and ~5% of all cancer deaths in 2019. The standard test for prostate cancer is the Prostate Serum Antigen (PSA) test. The PSA test suffers from low specificity (20-40%) in patients including ‘grey zone’ levels (4-10 ng/mL); moreover, the PSA test fails to identify patients with high-risk cancers. Previously we developed ExoDx Prostate Intelliscore (EPI), a urine-based exosome prostate cancer test optimized to rule out the need for a biopsy (risk stratification for high-grade prostate cancer). This study utilized a next generation exosome-based test that specifically enriches a subtype of prostate cancer exosomes from urine. Early detection of prostate cancer via a non-invasive method is desirable and the identification of patients with high-risk cancer is critical. Here we describe the development of a prostate-specific urinary exosome test for the identification of patients with prostate cancer. Methods: We have developed a prostate-specific enrichment method to isolate exosomes of prostate origin from urine samples. Using an affinity-based method against surface marker proteins found on prostate cells, we were able to selectively enrich for exosomes shed by the prostate gland with demonstrated specificity. Subsequent analysis of exosomal nucleic acids enables a promising panel of gene expression biomarkers capable of distinguishing patients with prostate cancer from healthy individuals. Results: RNA from prostate cancer enriched exosomes was compared to total exosomes from urine. Enrichment of prostate cancer specific exosomes significantly enhanced the RNA signature compared to total urine exosomes. Conclusions: Prostate cancer tests have recently been developed for RNA signatures in urine. Exosomes provide a source of nucleic acids as they are actively shed continuously from living cells as part of their normal life cycle. The urine exosomes can be used for total RNA transcriptome analysis and are therefore a very rich source of biomarkers for prostate cancer that can be tailored to different clinical indications. An affinity-based enrichment for tissue-specific exosomes allow for better resolution of the gene expression profile from the tissue of interest and reduces the RNA targets from non-relevant processes of the bladder and kidneys. The gene signature identified in this ongoing study could potentially provide a non-invasive molecular means for the early diagnosis of prostate cancer.

scholarly journals Urine Exosomes for Non-Invasive Assessment of Gene Expression and Mutations of Prostate Cancer

PLoS ONE ◽  
2016 ◽  
Vol 11 (5) ◽  
pp. e0154507 ◽  
Author(s):  
Piruz Motamedinia ◽  
Anna N. Scott ◽  
Kendall L. Bate ◽  
Neda Sadeghi ◽  
Guillermo Salazar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Non Invasive ◽  
Urine Exosomes

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.

Screening for prostate cancer

2017 ◽  
Author(s):  
Fritz H. Schröder
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Early Detection ◽  
Secondary Prevention ◽  
Current Knowledge ◽  
Age Groups ◽  
Population Based ◽  
High Rate ◽  
High Quality ◽  
Prostate Cancer Mortality

Screening for a disease must be clearly defined and differentiated from early detection. ‘Screening’ refers to the application of tests to the whole population or to defined segments such as males within certain defined high risk age groups. If applied in such a fashion ‘screening’ for prostate cancer may also be described epidemiologically as ‘secondary prevention’. While high-quality randomized studies show that screening reduces prostate cancer mortality by 21–44%, there is wide agreement that the introduction of population-based screening is at present premature because harms, mainly the high rate of overdiagnosis seen currently outweighs the benefits. This chapter attempts to put current knowledge into perspective with a set of recognized prerequirements for the application of screening, established by Wilson and Jungner in 1968.

scholarly journals Multiplex Gene Expression Profiling of In Vivo Isolated Circulating Tumor Cells in High-Risk Prostate Cancer Patients

2018 ◽  
Vol 64 (2) ◽  
pp. 297-306 ◽  
Author(s):  
Athina Markou ◽  
Marifili Lazaridou ◽  
Panagiotis Paraskevopoulos ◽  
Shukun Chen ◽  
Monika Świerczewska ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
High Risk ◽  
Expression Profiling ◽  
Stem Cell Markers ◽  
Epithelial Markers ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer ◽  
Emt Markers

Abstract BACKGROUND Molecular characterization of circulating tumor cells (CTCs) is important for selecting patients for targeted treatments. We present, for the first time, results on gene expression profiling of CTCs isolated in vivo from high-risk prostate cancer (PCa) patients compared with CTC detected by 3 protein-based assays—CellSearch®, PSA-EPISPOT, and immunofluorescence of CellCollector® in vivo-captured CTCs—using the same blood draw. METHODS EpCAM-positive CTCs were isolated in vivo using the CellCollector from 108 high-risk PCa patients and 36 healthy volunteers. For 27 patients, samples were available before and after treatment. We developed highly sensitive multiplex RT-qPCR assays for 14 genes (KRT19, EpCAM, CDH1, HMBS, PSCA, ALDH1A1, PROM1, HPRT1, TWIST1, VIM, CDH2, B2M, PLS3, and PSA), including epithelial markers, stem cell markers, and epithelial-to-mesenchymal-transition (EMT) markers. RESULTS We observed high heterogeneity in gene expression in the captured CTCs for each patient. At least 1 marker was detected in 74 of 105 patients (70.5%), 2 markers in 45 of 105 (40.9%), and 3 markers in 16 of 105 (15.2%). Epithelial markers were detected in 31 of 105 (29.5%) patients, EMT markers in 46 of 105 (43.8%), and stem cell markers in 15 of 105 (14.3%) patients. EMT-marker positivity was very low before therapy (2 of 27, 7.4%), but it increased after therapy (17 of 27, 63.0%), whereas epithelial markers tended to decrease after therapy (2 of 27, 7.4%) compared with before therapy (13 of 27, 48.1%). At least 2 markers were expressed in 40.9% of patients, whereas the positivity was 19.6% for CellSearch, 38.1% for EPISPOT, and 43.8% for CellCollector-based IF-staining. CONCLUSIONS The combination of in vivo CTC isolation with downstream RNA analysis is highly promising as a high-throughput, specific, and ultrasensitive approach for multiplex liquid biopsy-based molecular diagnostics.

scholarly journals Prognostic significance of the evaluation of expression of the gene PCA3 in urine in patients with localized prostate cancer and histomorphological changes in the peritumoral zone

2018 ◽  
Vol 8 (3) ◽  
pp. 11-19
Author(s):  
Philip S. Bova
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Biochemical Recurrence ◽  
Prognostic Significance ◽  
Intraepithelial Neoplasia ◽  
Disease Recurrence ◽  
Localized Prostate Cancer ◽  
Urine Sediment ◽  
Increased Risk ◽  
Urine Exosomes

Aim. To determine the prognostic significance PCA3 gene expression in urine sediment and exosomes in patients with localized prostate cancer (PC) and associated histologic changes in the peritumoral zone as a predictor of biochemical recurrence after radical prostatectomy (RPE). Materials and methods. Of 148 patients with localized PC, 96 (65%) had high-grade prostatic intraepithelial neoplasia (PIN-2) in the peritumoral zone. The other 52 (35%) had no pathologic tissue of the peritumoral zone. PDA3 expression in urine sediment and exosomes was determined with real-time PCR with respect to the reference gene KLK3. Results. The PCA3 gene expression level in urine exosomes in patients with PIN-2 in the prostatic peritumoral zone and synchronous pancreatic adenocarcinoma was higher among patients with subsequent disease recurrence. Increased PCA3 gene expression in the urine sediment was also predictive of the risk of recurrence of a prostatic tumor with PIN-2 in the peritumoral zone, although to a lesser degree than the results with urine exosomes. When the ∆Ct РСА3-KLK3 was ≥1,86 in the urine sediment, biochemical recurrence of PC and PIN-2 developed more frequently in the peritumoral zone (84% versus 51%, p = 0,013). Conclusions. Increased PCA3 gene expression in urine sediment and exosomes is a predictor of increased risk of biochemical recurrence after RPE in patients with localized PC and PIN-2 in the peritumoral zone.

scholarly journals Genome-wide mapping of 5-hydroxymethylcytosines in circulating cell-free DNA as a non-invasive approach for early detection of hepatocellular carcinoma

Gut ◽  
2019 ◽  
Vol 68 (12) ◽  
pp. 2195-2205 ◽  
Author(s):  
Jiabin Cai ◽  
Lei Chen ◽  
Zhou Zhang ◽  
Xinyu Zhang ◽  
Xingyu Lu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Early Detection ◽  
Diagnostic Model ◽  
Invasive Approach ◽  
Non Invasive ◽  
Free Dna ◽  
Genome Wide ◽  
Early Hcc ◽  
Validation Set

ObjectiveThe lack of highly sensitive and specific diagnostic biomarkers is a major contributor to the poor outcomes of patients with hepatocellular carcinoma (HCC). We sought to develop a non-invasive diagnostic approach using circulating cell-free DNA (cfDNA) for the early detection of HCC.DesignApplying the 5hmC-Seal technique, we obtained genome-wide 5-hydroxymethylcytosines (5hmC) in cfDNA samples from 2554 Chinese subjects: 1204 patients with HCC, 392 patients with chronic hepatitis B virus infection (CHB) or liver cirrhosis (LC) and 958 healthy individuals and patients with benign liver lesions. A diagnostic model for early HCC was developed through case-control analyses using the elastic net regularisation for feature selection.ResultsThe 5hmC-Seal data from patients with HCC showed a genome-wide distribution enriched with liver-derived enhancer marks. We developed a 32-gene diagnostic model that accurately distinguished early HCC (stage 0/A) based on the Barcelona Clinic Liver Cancer staging system from non-HCC (validation set: area under curve (AUC)=88.4%; (95% CI 85.8% to 91.1%)), showing superior performance over α-fetoprotein (AFP). Besides detecting patients with early stage or small tumours (eg, ≤2.0 cm) from non-HCC, the 5hmC model showed high capacity for distinguishing early HCC from high risk subjects with CHB or LC history (validation set: AUC=84.6%; (95% CI 80.6% to 88.7%)), also significantly outperforming AFP. Furthermore, the 5hmC diagnostic model appeared to be independent from potential confounders (eg, smoking/alcohol intake history).ConclusionWe have developed and validated a non-invasive approach with clinical application potential for the early detection of HCC that are still surgically resectable in high risk individuals.

226: Gene Expression / Biochemical Pathway Signatures of Prostate Cancer Cells of Patients with High Risk and Moderate Risk Progression of Disease

2005 ◽  
Vol 173 (4S) ◽  
pp. 62-62
Author(s):  
Syed Shaheduzzaman ◽  
Bungo Furusato ◽  
Vasantha Srikantan ◽  
Gyorgy Petrovics ◽  
Martin E. Nau ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
High Risk ◽  
Cancer Cells ◽  
Biochemical Pathway ◽  
Prostate Cancer Cells ◽  
Moderate Risk ◽  
Progression Of Disease
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