scholarly journals Assessment of miR-98-5p, miR-152-3p, miR-326 and miR-4289 Expression as Biomarker for Prostate Cancer Diagnosis

2019 ◽  
Vol 20 (5) ◽  
pp. 1154 ◽  
Author(s):  
Leire Moya ◽  
Jonelle Meijer ◽  
Sarah Schubert ◽  
Farhana Matin ◽  
Jyotsna Batra
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Specific Antigen ◽  
Area Under The Curve ◽  
High Specificity ◽  
Overall Survival Rate ◽  
Non Invasive ◽  
Specificity And Sensitivity ◽  
Depth Analysis ◽  
The Us

Prostate cancer (PCa) is one of the most commonly diagnosed cancers worldwide, accounting for almost 1 in 5 new cancer diagnoses in the US alone. The current non-invasive biomarker prostate specific antigen (PSA) has lately been presented with many limitations, such as low specificity and often associated with over-diagnosis. The dysregulation of miRNAs in cancer has been widely reported and it has often been shown to be specific, sensitive and stable, suggesting miRNAs could be a potential specific biomarker for the disease. Previously, we identified four miRNAs that are significantly upregulated in plasma from PCa patients when compared to healthy controls: miR-98-5p, miR-152-3p, miR-326 and miR-4289. This panel showed high specificity and sensitivity in detecting PCa (area under the curve (AUC) = 0.88). To investigate the specificity of these miRNAs as biomarkers for PCa, we undertook an in depth analysis on these miRNAs in cancer from the existing literature and data. Additionally, we explored their prognostic value found in the literature when available. Most studies showed these miRNAs are downregulated in cancer and this is often associated with cancer progression and poorer overall survival rate. These results suggest our four miRNA signatures could potentially become a specific PCa diagnostic tool of which prognostic potential should also be explored.

In1-ghrelin splicing variant as a key element in the pathophysiological association between obesity and prostate cancer

2021 ◽  
Author(s):  
Juan M Jiménez-Vacas ◽  
Antonio J Montero-Hidalgo ◽  
Enrique Gómez-Gómez ◽  
Antonio C Fuentes-Fayos ◽  
Francisco Ruiz-Pino ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Specificity ◽  
Metabolic Status ◽  
Grey Zone ◽  
Clinical Value ◽  
Related Factors ◽  
Clinical Model ◽  
Non Invasive ◽  
Splicing Variant ◽  
Specificity And Sensitivity

Abstract Context Recent studies emphasize the importance of considering the metabolic status to develop personalized medicine approaches. This is especially relevant in prostate cancer (PCa), wherein the diagnostic capability of PSA dramatically drops when considering patients with PSA levels ranging 3-10 ng/mL, the so-called “grey-zone”. Hence, additional non-invasive diagnostic and/or prognostic PCa biomarkers are urgently needed, especially in the metabolic-status context. Objective To assess the potential relation of urine In1-ghrelin (a ghrelin splicing variant) levels with metabolic-related/pathological conditions (e.g. obesity/diabetes/BMI/insulin-glucose levels), and to define its potential clinical value in PCa (diagnostic/prognostic capacity) and relationship with PCa-risk in patients with PSA in the grey-zone. Methods Urine In1-ghrelin levels were measured by radioimmunoassay in a clinically/metabolically/pathologically well-characterized cohort of patients without (n=397) or with (n=213) PCa with PSA in the grey-zone. Results Key obesity-related factors associated with PCa-risk (BMI/diabetes/glucose/insulin) were strongly correlated to In1-ghrelin levels. Importantly, In1-ghrelin levels were higher in PCa patients compared to control patients (with suspect of PCa but negative-biopsy). Moreover, high In1-ghrelin levels were associated with increased PCa-risk and linked to PCa-aggressiveness (e.g. tumour-stage/lymphovascular-invasion). In1-ghrelin levels added significant diagnostic value to a clinical model consisting of age, suspicious-DRE, previous-biopsy, and PSA levels. Furthermore, a multivariate model consisting of clinical and metabolic variables, including In1-ghrelin levels, showed high specificity and sensitivity to diagnose PCa (AUC=0.740). Conclusions Urine In1-ghrelin levels are associated with obesity-related factors and PCa risk/aggressiveness, and could represent a novel and valuable non-invasive PCa biomarker, as well as a potential link in the pathophysiological relationship between obesity and PCa.

Efficacy of Combination Chemotherapy With Docetaxel, Estramustine and Carboplatin in Men With Castration-resistant Prostate Cancer

2021 ◽  
Vol 1 (5) ◽  
pp. 451-457
Author(s):  
KATSUYA HIKITA ◽  
MASASHI HONDA ◽  
RYUTARO SHIMIZU ◽  
SHOGO TERAOKA ◽  
BUNYA KAWAMOTO ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Cancer Progression ◽  
Specific Antigen ◽  
Treatment Protocol ◽  
Area Under The Curve ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant

Background: The efficacy of docetaxel and carboplatin with oral estramustine was evaluated in patients with castration-resistant prostate cancer. Patients and Methods: Patients were treated with intravenous docetaxel at 30 mg/m2 on days 1, 8, 15, and 22 of a 28-day cycle. Intravenous carboplatin (area under the curve, 6 mg/ml/min) was administered on day 1. Patients received oral estramustine at 626.8 mg/day throughout the treatment protocol. Patients were evaluated for response, with treatment continued until cancer progression or onset of severe adverse events. Results: Twenty patients with castration-resistant prostate cancer were treated for a median of 3.5 cycles. Prostate-specific antigen decreased by more than 30% in 18 patients, including 14 patients with a decrease of more than 50%. Median overall survival was 11 months, prostate-specific antigen progression-free survival was 6.5 months, and radiographic progression-free survival was 7 months. Conclusion: Docetaxel and carboplatin with oral estramustine shows efficacy against castration-resistant prostate cancer.

scholarly journals Non-invasive Prostate Cancer Detection by Measuring Expression Level of miR-21 and miR-214 in Urine

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Alireza Emamvirdizadeh ◽  
Faranak Jamshidian ◽  
Maliheh Entezari ◽  
Saghi Nooraei ◽  
Mehrdad Hashemi
Keyword(s):  
Prostate Cancer ◽  
Sensitivity And Specificity ◽  
Healthy Subjects ◽  
Specific Antigen ◽  
Area Under The Curve ◽  
High Sensitivity ◽  
Expression Level ◽  
Control Group ◽  
Non Invasive ◽  
Invasive Method

Background: Prostate cancer is the most prevalent cancer among men worldwide. Diagnosis in this cancer is primarily done, using aggressive methods such as biopsy. Laboratory methods, such as the measurement of prostate-specific antigen (PSA) in the blood, do not have high sensitivity and specificity. MicroRNAs (miRNAs), a group of diagnostic biomarkers, can diagnose diseases such as cancer. MicroRNA (miRNA) is a small, non-coding, single-stranded RNA with a length of 21 to 23 nucleotides. Objectives: This study was designed to investigate the changes in the expression level of miR-21 and miR-214 in the urine of patients with prostate cancer compared with healthy controls. Methods: A total of 70 urine samples from prostate cancer patients (32 metastatic and 38 non-metastatic) and 30 from healthy subjects with negative biopsy reports were collected. The expression level of miR-21 and miR-214 in the urine were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Results: miR-21 showed a significant increase in expression (P = 0.003) and miR-214 showed a significant decrease in expression (P = 0.000) compared with the control group. The specificity, sensitivity, and area under the curve (AUC) were 100, 72.14, and 0.721% for combined panels of miR-21 and miR-214 and 63.33, 61.43, and 0.620%, respectively, for PSA. Conclusions: miR-21 and miR-214 showed significant change in expression in patients with prostate cancer compared with healthy subjects. It is hoped that, with further research, a combined panel of miR-21 and miR-214 can be used as a non-invasive method for detecting prostate cancer with higher sensitivity and specificity than the PSA test.

scholarly journals MicroRNA-940 as a Potential Serum Biomarker for Prostate Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Smrithi Rajendiran ◽  
Sayantan Maji ◽  
Ahmed Haddad ◽  
Yair Lotan ◽  
Rajesh R. Nandy ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Characteristic Curve ◽  
Specific Antigen ◽  
Cancer Prognosis ◽  
High Survival ◽  
Non Invasive ◽  
Non Coding Rnas ◽  
Clinically Significant ◽  
Culture Supernatants

Prostate cancer is one of the leading causes of death despite an astoundingly high survival rate for localized tumors. Though prostate specific antigen (PSA) test, performed in conjunction with digital rectal examinations, is reasonably accurate, there are major caveats requiring a thorough assessment of risks and benefits prior to conducting the test. MicroRNAs, a class of small non-coding RNAs, are stable molecules that can be detected in circulation by non-invasive methods and have gained importance in cancer prognosis and diagnosis in the recent years. Here, we investigate circulating miR-940, a miRNA known to play a role in prostate cancer progression, in both cell culture supernatants as well as patient serum and urine samples to determine the utility of miR-940 as a new molecular marker for prostate cancer detection. We found that miR-940 was significantly higher in serum from cancer patients, specifically those with clinically significant tumors (GS ≥ 7). Analysis of receiver operating characteristic curve demonstrated that miR-940 in combination with PSA had a higher area under curve value (AUC: 0.818) than the miR-940 alone (AUC: 0.75) for the diagnosis of prostate cancer. This study provides promising results suggesting the use of miR-940 for prostate cancer diagnosis.

scholarly journals Integrin Alpha V in Urine: A Novel Noninvasive Marker for Prostate Cancer Detection

2021 ◽  
Vol 10 ◽  
Author(s):  
Marina Y. Zemskova ◽  
Maria V. Marinets ◽  
Andrey V. Sivkov ◽  
Julia V. Pavlova ◽  
Andrey N. Shibaev ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Urine Analysis ◽  
Specific Antigen ◽  
High Specificity ◽  
Control Group ◽  
Prostate Hyperplasia ◽  
Non Invasive ◽  
Diagnostic Potential ◽  
Noninvasive Biomarker ◽  
Benign Prostate

Prostate cancer (PCa) diagnosis based on patient urine analysis provides non-invasive and promising method as compared to biopsy and a prostate-specific antigen (PSA) test. This study was conceived to investigate whether Integrin alpha V (ITGAV) protein is present in urine and assess the urinary ITGAV diagnostic potential for PCa. Materials and Methods: Urinary ITGAV expression was determined by Western blot analysis and quantified by ELISA in urine from men with PCa (n = 47), benign prostate hyperplasia (n = 42) and age-matched controls (n = 22). Results: The level of ITGAV protein was significantly lower in PCa urine samples as compared to those in the control group (p < 0.00001). The decrease of ITGAV in urine was highly predictive of PCa with 91.5% sensitivity, 91.4% specificity, 0.93 area under the ROC curve, and its specificity was better than that of serum PSA. Conclusion: Urinary ITGAV provides a novel noninvasive biomarker with high specificity.

scholarly journals Study of prostate cancer-derived extracellular vesicles in urine using IR spectroscopy

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Xin-Le Yap ◽  
Teng-Aik Ong ◽  
Jasmine Lim ◽  
Bayden Wood ◽  
Wai-Leng Lee
Keyword(s):  
Prostate Cancer ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Specific Antigen ◽  
Attenuated Total Reflection ◽  
Urine Samples ◽  
Early Screening ◽  
Linear Discriminant ◽  
Non Invasive ◽  
Potential Biomarker

Prostate cancer (PCa) is the third most frequent cancer in men and prostate-specific antigen is currently the biomarker used despite its low specificity. Lately, extracellular vesicles (EVs) which are secreted by all types of cells have raised research interest for their association with cancer progression. Urinary EVs UEVs) has emerged as a potential biomarker for PCa detection as it is non-invasive and urine samples are easily obtained from patients. Therefore, we hypothesize that PCa cells secrete EVs containing a unique set of biomolecules which can be exploited as a signature profile of the cancer. In this study, Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) spectroscopy was used for analysis of the UEVs aiming to obtain a signature spectrum for early detection of PCa. Urine samples from PCa and healthy subjects were subjected to ultracentrifugation for isolation of UEVs. Principal Component Analysis (PCA) indicated that FTIR spectra of the UEVs of PCa patients are distinct from those of healthy individuals at the following wavenumber values: amide I peak (1640 cm-1), RNA ribose peak (1120 cm-1), C-C, C-N stretch peak (967 cm-1) and C4–C5/C=N, imidazole ring peak (1610 cm-1). The obtained IR spectra were also analyzed using Linear Discriminant Analysis (LDA) and the resulting diagnostic classifier for PCa achieved a sensitivity of 83.33% and a specificity of 60%. In conclusion, ATR-FTIR analysis of UEVs in combine with PCA-LDA statistic model described in this study may offer a novel strategy for the development of a non-invasive urine test for early screening of prostate cancer.

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 Biofluid quantification of TWEAK/Fn14 axis in combination with a selected biomarker panel improves assessment of prostate cancer aggressiveness

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Xavier Ruiz-Plazas ◽  
Esther Rodríguez-Gallego ◽  
Marta Alves ◽  
Antonio Altuna-Coy ◽  
Javier Lozano-Bartolomé ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Biochemistry ◽  
Specific Antigen ◽  
Total Serum ◽  
Mrna Levels ◽  
Biomarker Panel ◽  
Non Invasive ◽  
Clinical Biomarkers ◽  
Cancer Aggressiveness ◽  
Aggressive Tumors

Abstract Background Conventional clinical biomarkers cannot accurately differentiate indolent from aggressive prostate cancer (PCa). We investigated the usefulness of a biomarker panel measured exclusively in biofluids for assessment of PCa aggressiveness. Methods We collected biofluid samples (plasma/serum/semen/post-prostatic massage urine) from 98 patients that had undergone radical prostatectomy. Clinical biochemistry was performed and several cytokines/chemokines including soluble(s) TWEAK, sFn14, sCD163, sCXCL5 and sCCL7 were quantified by ELISA in selected biofluids. Also, the expression of KLK2, KLK3, Fn14, CD163, CXCR2 and CCR3 was quantified by real-time PCR in semen cell sediment. Univariate, logistic regression, and receiver operating characteristic (ROC) analyses were used to assess the predictive ability of the selected biomarker panel in conjunction with clinical and metabolic variables for the evaluation of PCa aggressiveness. Results Total serum levels of prostate-specific antigen (PSA), semen levels of sTWEAK, fasting glycemia and mRNA levels of Fn14, KLK2, CXCR2 and CCR3 in semen cell sediment constituted a panel of markers that was significantly different between patients with less aggressive tumors [International Society of Urological Pathology (ISUP) grade I and II] and those with more aggressive tumors (ISUP grade III, IV and V). ROC curve analysis showed that this panel could be used to correctly classify tumor aggressiveness in 90.9% of patients. Area under the curve (AUC) analysis revealed that this combination was more accurate [AUC = 0.913 95% confidence interval (CI) 0.782–1] than a classical non-invasive selected clinical panel comprising age, tumor clinical stage (T-classification) and total serum PSA (AUC = 0.721 95% CI 0.613–0.830). Conclusions TWEAK/Fn14 axis in combination with a selected non-invasive biomarker panel, including conventional clinical biochemistry, can improve the predictive power of serum PSA levels and could be used to classify PCa aggressiveness.

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.

scholarly journals NMR-Based Metabolomic Profiling of Urine: Evaluation for Application in Prostate Cancer Detection

2019 ◽  
Vol 14 (5) ◽  
pp. 1934578X1984997 ◽  
Author(s):  
Neil MacKinnon ◽  
Wencheng Ge ◽  
Peisong Han ◽  
Javed Siddiqui ◽  
John T. Wei ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Area Under The Curve ◽  
Clinical Test ◽  
H Nmr ◽  
Metabolomic Profiling ◽  
Potential Biomarker ◽  
Noninvasive Biomarker ◽  
Auc Value ◽  
Selection Of

Detection of prostate cancer (PCa) and distinguishing indolent versus aggressive forms of the disease is a critical clinical challenge. The current clinical test is circulating prostate-specific antigen levels, which faces particular challenges in cancer diagnosis in the range of 4 to 10 ng/mL. Thus, a concerted effort toward building a noninvasive biomarker panel has developed. In this report, the hypothesis that nuclear magnetic resonance (NMR)-derived metabolomic profiles measured in the urine of biopsy-negative versus biopsy-positive individuals would nominate a selection of potential biomarker signals was investigated. 1H NMR spectra of urine samples from 317 individuals (111 biopsy-negative, 206 biopsy-positive) were analyzed. A double cross-validation partial least squares-discriminant analysis modeling technique was utilized to nominate signals capable of distinguishing the two classes. It was observed that after variable selection protocols were applied, a subset of 29 variables produced an area under the curve (AUC) value of 0.94 after logistic regression analysis, whereas a “master list” of 18 variables produced a receiver operating characteristic ROC) AUC of 0.80. As proof of principle, this study demonstrates the utility of NMR-based metabolomic profiling of urine biospecimens in the nomination of PCa-specific biomarker signals and suggests that further investigation is certainly warranted.

Sign in / Sign up

Export Citation Format

Share Document