scholarly journals MiR-93/miR-375: Diagnostic Potential, Aggressiveness Correlation and Common Target Genes in Prostate Cancer

2020 ◽  
Vol 21 (16) ◽  
pp. 5667
Author(s):  
Ewa Ciszkowicz ◽  
Paweł Porzycki ◽  
Małgorzata Semik ◽  
Ewa Kaznowska ◽  
Mirosław Tyrka
Keyword(s):  
Prostate Cancer ◽  
Operating Characteristic ◽  
Target Genes ◽  
Diagnostic Value ◽  
Tissue Samples ◽  
Non Invasive ◽  
Diagnostic Potential ◽  
Diagnostic Applications ◽  
First Time ◽  
Common Target

Dysregulation of miRNAs has a fundamental role in the initiation, development and progression of prostate cancer (PCa). The potential of miRNA in gene therapy and diagnostic applications is well documented. To further improve miRNAs’ ability to distinguish between PCa and benign prostatic hyperplasia (BPH) patients, nine miRNA (-21, -27b, -93, -141, -205, -221, -182, -375 and let-7a) with the highest reported differentiation power were chosen and for the first time used in comparative studies of serum and prostate tissue samples. Spearman correlations and response operating characteristic (ROC) analyses were applied to assess the capability of the miRNAs present in serum to discriminate between PCa and BPH patients. The present study clearly demonstrates that miR-93 and miR-375 could be taken into consideration as single blood-based non-invasive molecules to distinguish PCa from BPH patients. We indicate that these two miRNAs have six common, PCa-related, target genes (CCND2, MAP3K2, MXI1, PAFAH1B1, YOD1, ZFYVE26) that share the molecular function of protein binding (GO:0005515 term). A high diagnostic value of the new serum derived miR-182 (AUC = 0.881, 95% confidence interval, CI = 0.816–0.946, p < 0.0001, sensitivity and specificity were 85% and 79%, respectively) is also described.

scholarly journals Evaluation of MicroRNAs as Non-Invasive Diagnostic Markers in Urinary Cells from Patients with Suspected Prostate Cancer

Diagnostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 578
Author(s):  
Angelika Borkowetz ◽  
Andrea Lohse-Fischer ◽  
Jana Scholze ◽  
Ulrike Lotzkat ◽  
Christian Thomas ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Molecular Markers ◽  
Diagnostic Performance ◽  
Operating Characteristic ◽  
Clinical Performance ◽  
Diagnostic Value ◽  
Non Invasive ◽  
Diagnostic Potential ◽  
Specificity And Sensitivity ◽  
Diagnostic Power

Currently used tumor markers for early diagnosis of prostate cancer (PCa) are often lacking sufficient specificity and sensitivity. Therefore, the diagnostic potential of selected microRNAs in comparison to serum PSA levels and PSA density (PSAD) was explored. A panel of 12 PCa-associated microRNAs was quantified by qPCR in urinary sediments from 50 patients with suspected PCa undergoing prostate biopsy, whereupon PCa was detected in 26 patients. Receiver operating characteristic (ROC) curve analyses revealed a potential for non-invasive urine-based PCa detection for miR-16 (AUC = 0.744, p = 0.012; accuracy = 76%) and miR-195 (AUC = 0.729, p = 0.017; accuracy = 70%). While serum PSA showed an insufficient diagnostic value (AUC = 0.564, p = 0.656; accuracy = 50%) in the present cohort, PSAD displayed an adequate diagnostic performance (AUC = 0.708, p = 0.031; accuracy = 70%). Noteworthy, the combination of PSAD with the best candidates miR-16 and miR-195 either individually or simultaneously improved the diagnostic power (AUC = 0.801–0.849, p < 0.05; accuracy = 76–90%). In the sub-group of patients with PSA ≤ 10 ng/mL (n = 34), an inadequate diagnostic power of PSAD alone (AUC = 0.595, p = 0.524; accuracy = 68%) was markedly surpassed by miR-16 and miR-195 individually as well as by their combination with PSAD (AUC = 0.772–0.882, p < 0.05; accuracy = 74–85%). These findings further highlight the potential of urinary microRNAs as molecular markers with high clinical performance. Overall, these results need to be validated in a larger patient cohort.

scholarly journals Tumor-Derived Exosomal Long Noncoding RNAs as Promising Diagnostic Biomarkers for Prostate Cancer

2018 ◽  
Vol 46 (2) ◽  
pp. 532-545 ◽  
Author(s):  
Yu-Hui Wang ◽  
Jia Ji ◽  
Bi-Cheng Wang ◽  
Hao Chen ◽  
Zhong-Hua Yang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Invasion ◽  
Operating Characteristic ◽  
Specific Antigen ◽  
Roc Curves ◽  
Diagnostic Value ◽  
Healthy Individuals ◽  
Diagnostic Biomarkers ◽  
Non Invasive ◽  
Non Coding Rnas

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.

Three plasma-based microRNAs as potent diagnostic biomarkers for endometrial cancer

2021 ◽  
pp. 1-12
Author(s):  
Xingchen Fan ◽  
Minmin Cao ◽  
Cheng Liu ◽  
Cheng Zhang ◽  
Chunyu Li ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
External Validation ◽  
Diagnostic Value ◽  
Diagnostic Biomarkers ◽  
Non Invasive ◽  
Polymerase Chain ◽  
Public Datasets ◽  
Plasma Mirnas

BACKGROUND: MicroRNAs (miRNAs), with noticeable stability and unique expression pattern in plasma of patients with various diseases, are powerful non-invasive biomarkers for cancer detection including endometrial cancer (EC). OBJECTIVE: The objective of this study was to identify promising miRNA biomarkers in plasma to assist the clinical screening of EC. METHODS: A total of 93 EC and 79 normal control (NC) plasma samples were analyzed using Quantitative Real-time Polymerase Chain Reaction (qRT-PCR) in this four-stage experiment. The receiver operating characteristic curve (ROC) analysis was conducted to evaluate the diagnostic value. Additionally, the expression features of the identified miRNAs were further explored in tissues and plasma exosomes samples. RESULTS: The expression of miR-142-3p, miR-146a-5p, and miR-151a-5p was significantly overexpressed in the plasma of EC patients compared with NCs. Areas under the ROC curve of the 3-miRNA signature were 0.729, 0.751, and 0.789 for the training, testing, and external validation phases, respectively. The diagnostic performance of the identified signature proved to be stable in the three public datasets and superior to the other miRNA biomarkers in EC diagnosis. Moreover, the expression of miR-151a-5p was significantly elevated in EC plasma exosomes. CONCLUSIONS: A signature consisting of 3 plasma miRNAs was identified and showed potential for the non-invasive diagnosis of EC.

scholarly journals Integration of Urinary EN2 Protein & Cell-Free RNA Data in the Development of a Multivariable Risk Model for the Detection of Prostate Cancer Prior to Biopsy

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2102
Author(s):  
Shea Connell ◽  
Robert Mills ◽  
Hardev Pandha ◽  
Richard Morgan ◽  
Colin Cooper ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Model ◽  
Action Plan ◽  
Digital Rectal Examination ◽  
Standards Of Care ◽  
Net Benefit ◽  
Protein Levels ◽  
Non Invasive ◽  
Trus Biopsy ◽  
Diagnostic Potential

The objective is to develop a multivariable risk model for the non-invasive detection of prostate cancer prior to biopsy by integrating information from clinically available parameters, Engrailed-2 (EN2) whole-urine protein levels and data from urinary cell-free RNA. Post-digital-rectal examination urine samples collected as part of the Movember Global Action Plan 1 study which has been analysed for both cell-free-RNA and EN2 protein levels were chosen to be integrated with clinical parameters (n = 207). A previously described robust feature selection framework incorporating bootstrap resampling and permutation was applied to the data to generate an optimal feature set for use in Random Forest models for prediction. The fully integrated model was named ExoGrail, and the out-of-bag predictions were used to evaluate the diagnostic potential of the risk model. ExoGrail risk (range 0–1) was able to determine the outcome of an initial trans-rectal ultrasound guided (TRUS) biopsy more accurately than clinical standards of care, predicting the presence of any cancer with an area under the receiver operator curve (AUC) = 0.89 (95% confidence interval(CI): 0.85–0.94), and discriminating more aggressive Gleason ≥ 3 + 4 disease returning an AUC = 0.84 (95% CI: 0.78–0.89). The likelihood of more aggressive disease being detected significantly increased as ExoGrail risk score increased (Odds Ratio (OR) = 2.21 per 0.1 ExoGrail increase, 95% CI: 1.91–2.59). Decision curve analysis of the net benefit of ExoGrail showed the potential to reduce the numbers of unnecessary biopsies by 35% when compared to current standards of care. Integration of information from multiple, non-invasive biomarker sources has the potential to greatly improve how patients with a clinical suspicion of prostate cancer are risk-assessed prior to an invasive biopsy.

SOX9 stands for a bio-marker for prostate cancer detection

2020 ◽  
Author(s):  
Hao Zi ◽  
Wen-Lin Tao ◽  
Lei Gao ◽  
Zhao-Hua Yu ◽  
Xiao-Dong Bai ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Detection ◽  
Roc Curve ◽  
Operating Characteristic ◽  
Diagnostic Value ◽  
Quantitative Real Time Pcr ◽  
Optimal Cutoff ◽  
Qrt Pcr ◽  
Incidence And Mortality ◽  
The Relationship

Abstract Background Prostate cancer is one of common cancers around the world, and in our country the incidence and mortality of PCa are both increasing. More and more reports have revealed that SOX9 is involved in various human cancers. In this study, we aimed to explore the relationship between SOX9 expression and diagnostic value of PCa patients. Methods In this study, quantitative real-time PCR (qRT-PCR) was performed to determine the expression of SOX9 of the 131 PCa patients and 74 healthy volunteers. And receiver operating characteristic (ROC) curve was used to determine the diagnostic value of SOX9 for PCa patients. Results The results of qRT-PCR showed that the expression of serum SOX9 in PCa patients was higher than that in healthy controls (P < 0.05). And the expression of SOX9 was significantly associated with PSA (P = 0.001), differentiation (P = 0.000), and lymph node metastasis (P = 0.000). Besides, the area under the ROC curve (AUC) was 0.966 with the sensitivity of 93.2% and specificity of 87.8% respectively. The optimal cutoff value of SOX9 was 2.34. Conclusions Our results found that SOX9 is a novel oncogene for PCa, and may be a novel and effective biomarker for the diagnosis of patients with PCa.

The contribution of strain patterns in characterization of prostate peripheral zone lesions at transrectal ultrasonography

2012 ◽  
Vol 53 (1) ◽  
pp. 119-126 ◽  
Author(s):  
Yan Zhang ◽  
Jie Tang ◽  
Yan-mi Li ◽  
Xiang Fei ◽  
En-hui He ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Peripheral Zone ◽  
Diagnostic Value ◽  
Ultrasound Elastography ◽  
Transrectal Ultrasonography ◽  
Targeted Biopsy

Background Elasticity is an important characteristic of tissue. During an elastography examination, various strain images of lesions are observed, and a suitable classification of strain patterns (SP) may provide vital diagnostic information about lesions. Numerous studies have shown that ultrasound elastography can improve the detection of prostate cancer, but the diagnostic value of SP classification has not yet been fully evaluated. Purpose To investigate the contribution of SP on the characterization of prostate peripheral zone lesions by transrectal real-time tissue elastography (TRTE) in combination with conventional transrectal ultrasonography (TRUS). Material and Methods One hundred and seventy-one patients with suspected prostate cancer underwent TRUS and TRTE examinations. The SPs of the suspicious lesions were classified into five scores by TRTE according to the degree and distribution of strain. All findings were confirmed by transrectal systematic 12-core biopsies and targeted biopsies for suspicious areas detecting by TRUS and/or TRTE. Results One hundred and forty-eight of 171 patients had high-quality TRTE imaging and were included into the study. When a cut-off point of SP score III was used, the area under the receiver-operating characteristic curve (AUC) was, respectively, 0.75 (95% CI: 0.67–0.83), 0.85 (95% CI: 0.78–0.91) and 0.84 (95% CI: 0.77–0.91) for the diagnosis of prostate cancer by TRUS, TRTE and TRTE + TRUS. A linear tendency of SP and Gleason scores was observed in scores III-V. The detection rate of prostate cancer using TRTE-targeted biopsy (75.8%) was significantly higher than that of systematic 12-core biopsy plus TRUS-targeted biopsy (14.5%) ( P = 0.00). Conclusion This study suggests the significant contribution of SP on characterization of prostate peripheral zone lesions and the improvement of TRTE-targeted biopsy on detection of prostate cancer.

scholarly journals Role of miRNALet-7and Its Major Targets in Prostate Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Siegfried Wagner ◽  
Anaclet Ngezahayo ◽  
Hugo Murua Escobar ◽  
Ingo Nolte
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Target Genes ◽  
Prostate Cancer Screening ◽  
Prostate Gland ◽  
Specific Antigen ◽  
Current Treatment ◽  
Diagnostic Potential ◽  
Major Interest ◽  
Hormone Refractory

Prostate cancer is worldwide the sixth leading cause of cancer related death in men thus early detection and successful treatment are still of major interest. The commonly performed screening of the prostate-specific antigen (PSA) is controversially discussed, as in many patients the prostate-specific antigen levels are chronically elevated in the absence of cancer. Due to the unsatisfying efficiency of available prostate cancer screening markers and the current treatment outcome of the aggressive hormone refractory prostate cancer, the evaluation of novel molecular markers and targets is considered an issue of high importance. MicroRNAs are relatively stable in body fluids orchestrating simultaneously the expression of many genes. These molecules are currently discussed to bear a greater diagnostic potential than protein-coding genes, being additionally promising therapeutic drugs and/or targets. Herein we review the potential impact of the microRNAlet-7family on prostate cancer and show how deregulation of several of its target genes could influence the cellular equilibrium in the prostate gland, promoting cancer development as they do in a variety of other human malignant neoplasias.

scholarly journals Biomarker Potential of Plasma MicroRNA-150-5p in Prostate Cancer

Medicina ◽  
2019 ◽  
Vol 55 (9) ◽  
pp. 564 ◽  
Author(s):  
Ionut Andrei Paunescu ◽  
Razvan Bardan ◽  
Anca Marcu ◽  
Diana Nitusca ◽  
Alis Dema ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Area Under The Curve ◽  
Plasma Samples ◽  
Tissue Samples ◽  
New Class ◽  
Non Invasive ◽  
Plasma Microrna ◽  
Cancer Tissues ◽  
Tissue Cancer

Background and Objectives: Over decades, prostate cancer (PCa) has become one of the leading causes of cancer mortality in men. Extensive evidence exists that microRNAs (miRNAs or miRs) are key players in PCa and a new class of non-invasive cancer biomarkers. Materials and Methods: We performed miRNA profiling in plasma and tissues of PCa patients and attempted the validation of candidate individual miRs as biomarkers. Results: The comparison of tissue and plasma profiling results revealed five commonly dysregulated miRs, namely, miR-130a-3p, miR-145-5p, miR-148a-3p, miR-150-5p, and miR-365a-3p, of which only three show concordant changes—miR-130a-3p and miR-150-5p were downregulated and miR-148a-3p was upregulated in both tissue and plasma samples, respectively. MiR-150-5p was validated as significantly downregulated in both plasma and tissue cancer samples, with a fold change of −2.697 (p < 0.001), and −1.693 (p = 0.035), respectively. ROC analysis showed an area under the curve (AUC) of 0.817 (95% CI: 0.680–0.995) for plasma samples and 0.809 (95% CI: 0.616–1.001) for tissue samples. Conclusions: We provide data indicating that miR-150-5p plasma variations in PCa patients are associated with concordant changes in prostate cancer tissues; however, given the heterogeneous nature of previous findings of miR-150-5p expression in PCa cells, additional future studies of a larger sample size are warranted in order to confirm the biomarker potential and role of miRNA-150-5p in PCa biology.

Diagnostic performance of microRNAs in the circulation in differential diagnosis of BPH, chronic prostatitis and prostate cancer

2018 ◽  
Vol 44 (4) ◽  
pp. 417-425 ◽  
Author(s):  
Yakup Dülgeroğlu ◽  
Onur Eroğlu
Keyword(s):  
Prostate Cancer ◽  
Chronic Prostatitis ◽  
Diagnostic Performance ◽  
Serum Levels ◽  
Diagnostic Value ◽  
Prostatic Hyperplasia ◽  
Qrt Pcr ◽  
Cancer Group ◽  
Diagnostic Potential ◽  
Specificity And Sensitivity

Abstract Background In this study, the objective was to evaluate the diagnostic performance of some miRNAs, which were shown to have a diagnostic value for prostate cancer (PCa), and the effect of chronic prostatitis in distinguishing benign prostatic hyperplasia (BPH) and PCa. Materials and methods Serum levels of 11 miRNAs were investigated in BPH, chronic prostatitis and PCa patients. Measurements were performed using qRT-PCR. Results In the analysis, serum levels of miR-375, -125b-5p, -30c-5p, -26b-5p, and let-7c-5p were downregulated in cancer compared with non-cancer group and AUCs of these miRNAs in distinguishing PCa group from non-cancer group were calculated as 0.781, 0.782, 0.762, 0.874, and 0.845, respectively. AUC of the combination of miR-375 and miR-26b-5p in distinguishing PCa group from non-cancer group was 0.891, AUC of these two miRNAs in distinguishing PCa group from BPH group was 0.944. Conclusion In our study, 11 miRNAs were studied and 5 of these miRNAs were considered as biomarker candidates as these miRNAs, individually or combined, could be used to distinguish PCa from benign conditions. Furthermore, a higher specificity and sensitivity were obtained in distinguishing BPH and PCa when data for diagnostic potential of miRNAs were analyzed without including chronic prostatic group.

scholarly journals Liquid biopsy for patients with IBD-associated neoplasia

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hideaki Kinugasa ◽  
Sakiko Hiraoka ◽  
Kazuhiro Nouso ◽  
Shumpei Yamamoto ◽  
Mami Hirai ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Target Genes ◽  
Tumor Tissue ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Tissue Samples ◽  
Non Invasive ◽  
Tumor Tissues ◽  
Inflammatory Bowel

Abstract Background It is often difficult to diagnose inflammatory bowel disease (IBD)-associated neoplasia endoscopically due to background inflammation. In addition, due to the absence of sensitive tumor biomarkers, countermeasures against IBD-associated neoplasia are crucial. The purpose of this study is to develop a new diagnostic method through the application of liquid biopsy. Methods Ten patients with IBD-associated cancers and high-grade dysplasia (HGD) with preserved tumor tissue and blood were included. Tumor and non-tumor tissues were analyzed for 48 cancer-related genes using next-generation sequencing. Simultaneously, circulating tumor DNA (ctDNA) was analyzed for mutations in the target genes using digital PCR. Results Out of 10 patients, seven had IBD-related cancer and three had IBD-related HGD. Two patients had carcinoma in situ; moreover, three had stageII and two had stage III. To avoid false positives, the mutation rate cutoff was set at 5% based on the control results; seven of 10 (70%) tumor tissue samples were mutation-positive. Mutation frequencies for each gene were as follows: TP53 (20.9%; R136H), TP53 (25.0%; C110W), TP53 (8.5%; H140Q), TP53 (31.1%; R150W), TP53 (12.8%; R141H), KRAS (40.0%; G12V), and PIK3CA (34.1%; R 88Q). The same mutations were detected in the blood of these seven patients. However, no mutations were detected in the blood of the remaining three patients with no tumor tissue mutations. The concordance rate between tumor tissue DNA and blood ctDNA was 100%. Conclusion Blood liquid biopsy has the potential to be a new method for non-invasive diagnosis of IBD-associated neoplasia.

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