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 ◽  
...  

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.

2018 ◽  
Vol 46 (2) ◽  
pp. 532-545 ◽  
Author(s):  
Yu-Hui Wang ◽  
Jia Ji ◽  
Bi-Cheng Wang ◽  
Hao Chen ◽  
Zhong-Hua Yang ◽  
...  

Background/Aims: Exosomal circulating long non-coding RNAs (lncRNAs) in blood are emerging as clinically useful and non-invasive biomarkers for tumor diagnosis. However, normal cells can also secrete exosomes, so it is a prerequisite to obtain tumor-derived exosomes for better understanding of their diagnostic impacts in cancer. In this study, a dual-antibody-functionalized immunoaffinity system was established to isolate exosomes and investigate their lncRNAs expression pattern and clinical significance in prostate cancer (PCa). Methods: A commercially available kit was used to isolate total exosomes, which were then purified by a dual-antibody-functionalized immunoaffinity system. RT-qPCR was performed to detect the expression of exosomal lncRNAs. Receiver operating characteristic (ROC) curves were plotted to assess the diagnostic value. Results: Expression levels of two lncRNAs in tumor-derived exosomes were significantly higher than those in total exosomes. The levels of SAP30L-AS1 were upregulated in benign prostatic hyperplasia (BPH), and SChLAP1 levels were significantly higher in PCa than in BPH and healthy individuals. The area under the ROC curve indicated that SAP30L-AS1 and SChLAP1 had adequate diagnostic value to distinguish PCa from controls. Two lncRNAs separately combined with prostate specific antigen (PSA) possessed a moderate ability for discrimination. SAP30L-AS1 expression level was related to PSA values and tumor invasion. SChLAP1 expression was significantly higher in patients with higher Gleason scores, and was also effective in differentiating between BPH and PCa when the concentration of PSA was in the gray zone. Conclusion: The isolation of tumor-derived exosomes by dual-antibody-functionalized immunoaffinity systems and detection of their lncRNAs in plasma may lead to the identification of suitable biomarkers, with potential diagnostic utility.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Igor Yusim ◽  
Muhammad Krenawi ◽  
Elad Mazor ◽  
Victor Novack ◽  
Nicola J. Mabjeesh

AbstractThe purpose of this study was to assess the predictive value of prostate specific antigen density (PSAD) for detection of clinically significant prostate cancer in men undergoing systematic transrectal ultrasound (TRUS)-guided prostate biopsy. We retrospectively analyzed data of men who underwent TRUS-guided prostate biopsy because of elevated PSA (≤ 20 ng/ml) or abnormal digital rectal examination. Receiver operating characteristic curve analysis to compare PSA and PSAD performance and chi-square automatic interaction detector methodologies were used to identify predictors of clinically significant cancer (Gleason score ≥ 7 or international society of urological pathology grade group ≥ 2). Nine-hundred and ninety-two consecutive men with a median age of 66 years (IQR 61–71) were included in the study. Median PSAD was 0.10 ng/ml2 (IQR 0.10–0.22). Prostate adenocarcinoma was diagnosed in 338 men (34%). Clinically significant prostate adenocarcinoma was diagnosed in 167 patients (50% of all cancers and 17% of the whole cohort). The AUC to predict clinically significant prostate cancer was 0.64 for PSA and 0.78 for PSAD (P < 0.001). The highest Youden's index for PSAD was at 0.20 ng/ml2 with 70% sensitivity and 79% specificity for the diagnosis of clinically significant cancer. Men with PSAD < 0.09 ng/ml2 had only 4% chance of having clinically significant disease. The detection rate of clinically significant prostate cancer in patients with PSAD between 0.09 and 0.19 ng/ml2 was significantly higher when prostate volume was less than 33 ml. In conclusion, PSAD was a better predictor than PSA alone of clinically significant prostate cancer in patients undergoing TRUS-guided biopsy. Patients with PSAD below 0.09 ng/ml2 were unlikely to harbor clinically significant prostate cancer. Combining PSAD in the gray zone (0.09–0.19) with prostate volume below 33 ml adds diagnostic value of clinically significant prostate cancer.


2019 ◽  
Vol 20 (5) ◽  
pp. 1154 ◽  
Author(s):  
Leire Moya ◽  
Jonelle Meijer ◽  
Sarah Schubert ◽  
Farhana Matin ◽  
Jyotsna Batra

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.


Author(s):  
Xin-Le Yap ◽  
Teng-Aik Ong ◽  
Jasmine Lim ◽  
Bayden Wood ◽  
Wai-Leng Lee

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.


Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3373
Author(s):  
Milena Matuszczak ◽  
Jack A. Schalken ◽  
Maciej Salagierski

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.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Linghui Liang ◽  
Feng Qi ◽  
Yifei Cheng ◽  
Lei Zhang ◽  
Dongliang Cao ◽  
...  

AbstractTo analyze the clinical characteristics of patients with negative biparametric magnetic resonance imaging (bpMRI) who didn’t need prostate biopsies (PBs). A total of 1,012 male patients who underwent PBs in the First Affiliated Hospital of Nanjing Medical University from March 2018 to November 2019, of 225 had prebiopsy negative bpMRI (defined as Prostate Imaging Reporting and Data System (PI-RADS 2.1) score less than 3). The detection efficiency of clinically significant prostate cancer (CSPCa) was assessed according to age, digital rectal examination (DRE), prostate volume (PV) on bpMRI, prostate-specific antigen (PSA) and PSA density (PSAD). The definition of CSPCa for Gleason score > 6. Univariate and multivariable logistic regression analysis were used to identify predictive factors of absent CSPCa on PBs. Moreover, absent CSPCa contained clinically insignificant prostate cancer (CIPCa) and benign result. The detection rates of present prostate cancer (PCa) and CSPCa were 27.11% and 16.44%, respectively. Patients who were diagnosed as CSPCa had an older age (P < 0.001), suspicious DRE (P < 0.001), a smaller PV (P < 0.001), higher PSA value (P = 0.008) and higher PSAD (P < 0.001) compared to the CIPCa group and benign result group. PSAD < 0.15 ng/ml/cm3 (P = 0.004) and suspicious DRE (P < 0.001) were independent predictors of absent CSPCa on BPs. The negative forecast value of bpMRI for BP detection of CSPCa increased with decreasing PSAD, mainly in patients with naive PB (P < 0.001) but not in prior negative PB patients. 25.33% of the men had the combination of negative bpMRI, PSAD < 0.15 ng/ml/cm3 and PB naive, and none had CSPCa on repeat PBs. The incidence of PB was determined, CSPCa was 1.59%, 0% and 16.67% in patients with negative bpMRI and PSAD < 0.15 ng/ml/cm3, patients with negative bpMRI, PSAD < 0.15 ng/ml/cm3 and biopsy naive and patients with negative bpMRI, PSAD < 0.15 ng/ml/cm3 and prior negative PB, separately. We found that a part of patients with negative bpMRI, a younger age, no suspicious DRE and PSAD < 0.15 ng/ml/cm3 may securely avoid PBs. Conversely PB should be considered in patients regardless of negative bpMRI, especially who with a greater age, obviously suspicious DRE, significantly increased PSA value, a significantly small PV on MRI and PSAD > 0.15 ng/ml/cm3.


2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Xavier Ruiz-Plazas ◽  
Esther Rodríguez-Gallego ◽  
Marta Alves ◽  
Antonio Altuna-Coy ◽  
Javier Lozano-Bartolomé ◽  
...  

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.


2013 ◽  
Vol 3 (3) ◽  
pp. 205 ◽  
Author(s):  
Sandeep Mistry ◽  
Wesley Mayer ◽  
Rose Khavari ◽  
Gustavo Ayala ◽  
Brian Miles

Introduction: Prostate cancer is the most common nonskin malignancyaffecting men and is the second leading cause of cancerrelateddeath in North America. The incidence of prostate cancerincreases dramatically with age. However, many healthauthorities advocate the cessation of routine prostate cancer testingin men older than 75 because of the belief that most patientswill have a clinically insignificant cancer and will not benefit fromtherapy. The true prevalence of clinically significant prostate cancerin elderly men is not known.Methods: We analyzed 1446 needle biopsies of the prostate inmen aged 75 or older. All pathological reviews were conductedby the pathology department at the Methodist Hospital in Houston,Tex. Data were collected from pathology reports, hospital andclinic databases, and medical records when available. Dataobtained included age at biopsy, serum prostate-specific antigen(PSA) levels, number of positive core biopsies and Gleasongrade. Statistical analysis was performed using Stata. Clinicallysignificant cancer was defined by the pathological presence ofGleason grade 6 adenocarcinoma in more than 1 biopsy coreor the presence of any Gleason 4 or 5 component in the biopsy.Results: The median age of the patients included in the studywas 78.8 and 95% of the patients were between the ages of 75and 85. The mean serum PSA level for patients biopsied was10.4 μg/L. Of all biopsies reviewed, 53% were positive for prostatecancer and 78% of these would be defined as clinically significantcancer. Regression analysis revealed age to be a significant(p < 0.05) factor for increased Gleason grade in positive biopsies.Logistic regression revealed age as a significant factor (p <0.05) for clinically significant prostate cancer even when controllingfor PSA. A serum PSA threshold value of 6.5 μg/L would havemissed 38% of significant cancers and a threshold of 4.0 μg/Lwould have missed 8% of significant cancers.Conclusion: Our findings suggest that the prevalence of clinicallysignificant prostate cancer in the elderly population may be higherthan previously thought. As the population continues to livelonger and healthier lives, it will become more common to confrontprostate cancer morbidity in the eldery population. Usinghigher serum PSA thresholds to eliminate unnecessary biopsies inolder men does not appear to help identify patients at greaterrisk of having clinically significant prostate cancer. Patients withprostate cancer having aggressive clinical features may benefitfrom treatment of their prostate cancer well into their eighth andninth decades of life. Testing and diagnostic recommendationsshould reflect the potential benefit of identifying patients withaggressive prostate cancer even after age 75.Introduction : Le cancer de la prostate est le type de cancer noncutané le plus fréquent chez les hommes et la seconde causede décès lié au cancer en importance en Amérique du Nord.L’incidence du cancer de la prostate augmente grandement avecl’âge. Néanmoins, de nombreuses autorités en matière de santéavancent l’idée de mettre fin au dépistage systématique du cancerde la prostate chez les hommes de plus de 75 ans en raisonde la croyance selon laquelle la plupart des patients présenterontun cancer non significatif sur le plan clinique et ne bénéficierontpas d’un traitement. La véritable prévalence des cas decancer de la prostate cliniquement significatif chez les hommesâgés n’est pas établie.Méthodes : Nous avons analysé 1446 échantillons de biopsie àl’aiguille prélevés au niveau de la prostate chez des patients de75 ans ou plus. Toutes les analyses de pathologie ont été effectuéespar le service de pathologie du Methodist Hospital deHouston, au Texas. Les données ont été tirées des rapports depathologie, des bases de données des hôpitaux et des cliniques,et des dossiers médicaux lorsque possible. Les données obtenuesincluaient l’âge au moment de la biopsie, les valeurs d’antigèneprostatique spécifique (APS), le nombre de microbiopsies positiveset le score de Gleason. Les analyses statistiques ont été effectuéesà l’aide du système Stata. Le cancer cliniquement significatifest défini comme la présence d’un adénocarcinome avec un scorede Gleason de 6 dans plus d’une zone de biopsie ou un scorede Gleason de 4 ou 5 dans toute partie de l’échantillon.Résultats : L’âge moyen des patients inclus était de 78,8 ans et95 % des patients avaient entre 75 et 85 ans. La valeur moyennede l’APS chez les patients ayant subi une biopsie était de 10,4 μg/L.De tous les échantillons examinés, 53 % confirmaient la présenced’un cancer de la prostate, et le cancer était défini comme étantcliniquement significatif dans 78 % de ces cas. Une analyse derégression a révélé que l’âge était un facteur significatif (p <0,05) lié à un score de Gleason plus élevé dans les biopsies positives.Une analyse de régression logistique a révélé que l’âge étaitaussi un facteur significatif (p < 0,05) lié à un cancer de la prostatecliniquement significatif même en tenant compte du taux d’APS.Une valeur seuil d’APS de 6,5 μg/L serait passée à côté de 38 %des cas de cancer significatif, alors qu’une valeur seuil d’APSde 4,0 μg/L serait passée à côté de 8 % des cancers significatifs.Conclusion : Nos observations portent à croire que la prévalencedu cancer de la prostate significatif sur le plan clinique chezles patients âgés pourrait être plus élevée qu’on le croit. Avecl’augmentation de l’espérance de vie, l’incidence de la morbiditéliée au cancer de la prostate augmentera. Le recours àdes valeurs seuils d’APS plus élevées pour éliminer les cas debiopsies non nécessaires chez les hommes âgés ne semble pasaider à cerner les patients présentant un risque plus élevé de cancerde la prostate cliniquement significatif. Les patients atteintsde cancer de la prostate cliniquement agressif peuvent bénéficierd’un traitement contre le cancer même lorsqu’ils dépassentlargement les 80 ou les 90 ans. Les recommandations concernantle dépistage et le diagnostic devraient refléter les avantages potentielsliés au dépistage d’un cancer de la prostate agressif, mêmeaprès 75 ans.


2018 ◽  
Vol 12 (1) ◽  
pp. 13-19 ◽  
Author(s):  
Athanasios Skarmoutsos ◽  
Ioannis Skarmoutsos ◽  
Ioannis Katafigiotis ◽  
Elisavet Tataki ◽  
Athina Giagini ◽  
...  

Introduction: Although the prostate specific antigen revolutionized the diagnosis of prostate cancer (PCa), it has its limitations. We prospectively examined the potential use of the platelet-derived growth factor-BB (PDGF-BB) as a urine biomarker for the early diagnosis of PCa. Materials and Methods: The urine samples of 118 patients were collected after a prostatic massage and all the patients subsequently underwent ultrasound-guided transrectal biopsy. PDGF-BB was detected in the urine by enzyme-linked immunosorbent assay. Results: Patients with PCa had greater levels of prostate specific antigen and PDGF-BB. Receiver operating characteristic curve analysis showed that the optimal cut-of of PDGF-BB for the prediction of PCa was 1,504.9 with a sensitivity of 60% and a specificity of 51.3%. For a 100 unit increase in PDGF-BB, the likelihood for PCa increased about 4%. Conclusion: PDGF-BB showed a significant predictive ability for PCa. Detection of PDGF-BB in urine with Elisa was easy and improved our diagnostic accuracy in the diagnosis of PCa.


2021 ◽  
Author(s):  
Shotaro Nakanishi ◽  
Masato Goya ◽  
Mitsuyoshi Tamaki ◽  
Takuma Oshiro ◽  
Seiichi Saito

Abstract Objective: To date, there are no useful markers for predicting the prognosis of metastatic hormone-sensitive prostate cancer (mHSPC). We evaluated the effect of early changes in prostate-specific antigen (PSA) levels after androgen deprivation therapy (ADT) on castration-resistant prostate cancer (CRPC) progression and overall survival (OS) in mHSPC patients. Results: In 71 primary mHSPC patients treated with ADT, the median times to CRPC and OS were 15 months and 92 months, respectively. In multivariate analysis, a Gleason score of ≥8 (p = 0.004), an extent of disease value (EOD) of ≥2 (p = 0.004), and a 3-month PSA level >1% of the pretreatment level (p = 0.017) were independent predictors of shorter time to CRPC. The area under the receiver operating characteristic curve was feasible at 0.822. For OS, a 3-month PSA level >1% of the pretreatment level was an independent predictor of time to CRPC (p = 0.004).Three factors were independent predictors of shorter time to CRPC. A 3-month PSA level >1% of the pretreatment level correlated with poor a prognosis.


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