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

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.

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Non‑invasive prostate cancer detection by measuring expression level of miR-21 and miR-214 in urine

10.21203/rs.3.rs-44812/v1 ◽

2020 ◽

Author(s):

Alireza Emamvirdizadeh ◽

Faranak Jamshidian ◽

Mehrdad Hashemi ◽

Saghi Nooraei ◽

Maliheh Entezari

Keyword(s):

Prostate Cancer ◽

Sensitivity And Specificity ◽

Specific Antigen ◽

High Sensitivity ◽

Expression Level ◽

Control Group ◽

Non Invasive ◽

Invasive Method ◽

Detect Prostate Cancer ◽

Group A

Abstract 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 measurement of prostate specific antigen (PSA) in the blood, do not have high sensitivity and specificity. MicroRNAs, a group of diagnostic biomarkers, can be used to diagnose diseases such as cancer. MicroRNA is small, non-coding, single-stranded RNA with a length of 21-23 nucleotides. The present study was undertaken to investigate changes in the expression level of miR-21 and miR-214 in the urine to detect prostate cancer. Methods: Testing was done on 70 urine samples from prostate cancer patients (32 metastatic and 38 non-metastatic) and 30 from healthy individuals with negative biopsy reports as the control group. Changes in the expression level of miR-21 and miR-214 in the urine were investigated by using 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) over the results of the control group. The specificity, sensitivity and AUC for combined panels of both microRNAs were 100%, 72.14% and 0.721 and for PSA were 63.33%, 61.43% and 0.620, respectively. Conclusions: The results show that miR-21 and miR-214 show significant changes in expression in patients with prostate cancer compared to the control group. 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.

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Circulating miRNAs as Biomarkers for Prostate Cancer Diagnosis in Subjects with Benign Prostatic Hyperplasia

Journal of Immunology Research ◽

10.1155/2020/5873056 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Wei Jin ◽

Xiang Fei ◽

Xia Wang ◽

Fangjie Chen ◽

Yan Song

Keyword(s):

Prostate Cancer ◽

Benign Prostatic Hyperplasia ◽

Statistical Tests ◽

Specific Antigen ◽

Area Under The Curve ◽

Prostatic Hyperplasia ◽

Control Group ◽

Circulating Mirnas ◽

Noninvasive Biomarker ◽

Novel Biomarkers

Body fluids often contain freely circulating nucleic acids, many of which can be exploited as noninvasive tools for the diagnosis of cancer as well as for clinical prognostication. Identifying microRNAs (miRNAs) in subjects’ blood with various malignancies means that they can serve as novel biomarkers for prostate cancer (PCa) diagnosis. This study analyzed serum-circulating miRNAs as a noninvasive biomarker in subjects with PCa and subjects with benign prostatic hyperplasia (BPH). In total, 31 PCa subjects and 31 BPH subjects were included, with the BPH group serving as the control group. RT-qPCR was used to quantify the levels of 10 miRNAs, which included miR-18a, miR-34a, miR-106b, miR-183, miR-200a, miR-301a, miR-141, miR-182, miR-200b, and miR-375 in serum. Statistical tests were used to assess the relationship between the levels of miRNAs and the clinicopathological data. A significant increase was observed in the relative expression ratios of miR-141, miR-182, miR-200b, and miR-375 (1.89-, 2.09-, 2.41-, and 2.27-folds, respectively) in the PCa group when compared to the BPH group. Based on the receiver operating characteristic (ROC) analysis, the largest area under the curve (AUC), 0.923, was associated with the miR-200b group, indicating effective diagnostic properties for this biomarker. A correlation was observed between total prostate-specific antigen (TPSA) and the relative levels of miR-141, miR-182, miR-200b, and miR-375. The Gleason score and the miR-200b expression level were also correlated. These results are consistent with previous studies regarding the possibility of differentiating between PCa subjects and healthy controls based on the detection of miRNA. The findings attest to a distinctive expression profile of miRNA that is detectable in the blood of PCa subjects, thereby confirming the role of miRNAs as diagnostic biomarkers for PCa.

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Prostate-Specific Antigen Kinetics During Follow-Up Are an Unreliable Trigger for Intervention in a Prostate Cancer Surveillance Program

Journal of Clinical Oncology ◽

10.1200/jco.2009.25.7311 ◽

2010 ◽

Vol 28 (17) ◽

pp. 2810-2816 ◽

Cited By ~ 178

Author(s):

Ashley E. Ross ◽

Stacy Loeb ◽

Patricia Landis ◽

Alan W. Partin ◽

Jonathan I. Epstein ◽

...

Keyword(s):

Prostate Cancer ◽

Prostate Specific Antigen ◽

Sensitivity And Specificity ◽

Active Surveillance ◽

Gleason Score ◽

Specific Antigen ◽

Area Under The Curve ◽

Cancer Surveillance ◽

Surveillance Program

Purpose To assess the predictive ability of prostate-specific antigen (PSA) velocity (PSAV) and doubling time (PSADT) for biopsy progression and adverse pathology at prostatectomy among men with low-risk prostate cancer enrolled on an active-surveillance program. Methods We evaluated 290 men who met criteria for active surveillance (ie, PSA density < 0.15 ng/mL/cm3 and Gleason score ≤ 6 with no pattern ≥ 4, involving ≤ 2 cores with cancer, and ≤ 50% involvement of any core by cancer) with two or more serial PSA measurements after diagnosis from 1994 to 2008. Follow-up included twice-yearly digital rectal exam and PSA measurements and yearly surveillance biopsy. Treatment was recommended for biopsy progression (ie, Gleason score ≥ 7, or > 2 positive cores, or > 50% core involvement). Sensitivity and specificity of postdiagnostic PSAV and PSADT were explored by using receiver operating characteristic (ROC) analysis. Results Overall, 188 (65%) men remained on active surveillance, and 102 (35%) developed biopsy progression at a median follow-up of 2.9 years. PSADT was not significantly associated with subsequent adverse biopsy findings (P = .83), and PSAV was marginally significant (P = .06). No PSAV or PSADT cut point had both high sensitivity and specificity (area under the curve, 0.61 and 0.59, respectively) for biopsy progression. In those who eventually underwent radical prostatectomy, PSAV (P = .79) and PSADT (P = .87) were not associated with the presence of unfavorable surgical pathology. Conclusion Postdiagnostic PSA kinetics do not reliably predict adverse pathology and should not be used to replace annual surveillance biopsy for monitoring men on active surveillance.

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Voided urine test to diagnose prostate cancer: Preliminary report

CytoJournal ◽

10.25259/cytojournal_76_2020 ◽

2021 ◽

Vol 18 ◽

pp. 26

Author(s):

R.B. Nerli ◽

Shridhar C. Ghagane ◽

Saziya R. Bidi ◽

Madhukar L. Thakur ◽

Leonard Gomella

Keyword(s):

Prostate Cancer ◽

Specific Antigen ◽

Control Group ◽

Study Group ◽

Elderly Male ◽

Non Invasive ◽

Diagnose Prostate Cancer ◽

Preliminary Study ◽

Histopathological Studies ◽

Vasoactive Intestinal Peptide Receptor

Objectives: Prostate cancer (PCa) is a common malignancy affecting elderly male. At present, PCa is estimated using serum prostate-specific antigen (PSA). Prostate biopsy remains the gold standard to confirm the diagnosis of PCa. In this preliminary study, we have assessed the feasibility of detecting PCa using voided urine by targeting the genomic vasoactive intestinal peptide receptor (VPAC) expressed on malignant PCa cells. Material and Methods: Patients ≥40 years old, with no lower urinary tract symptoms (LUTS) and serum PSA levels of <1.6 ng/mL formed the control group and patients ≥40 years old, with LUTS and serum PSA >2.6 ng/ mL formed the study group. Patients were advised to give the first 50 mL of voided urine sample for the detection of malignant markers by targeting the VPAC. The results of histopathological studies were then compared to the results of urine biomarker. Results: The study revealed absence of malignant markers in 75 patients (control group). In the study group, all the 33 patients with adenocarcinoma were positive for malignant markers in the biomarker study and absence of malignant markers in the 32 patients with benign histology. The results of the biomarker studies and histopathology were consistent with each other. Conclusion: This preliminary study validates our belief that patients with PCa do shed malignant cells in the urine which can be identified by targeting the VPAC. The investigation is easy and our data appear to be highly encouraging and further serve as a simple, reliable, and a non-invasive tool in the detection of PCa.

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Correlation of Paraoxonase-1 with the Severity of Crohn’s Disease

Molecules ◽

10.3390/molecules23102603 ◽

2018 ◽

Vol 23 (10) ◽

pp. 2603

Author(s):

Katarzyna Szczeklik ◽

Tomasz Mach ◽

Dorota Cibor ◽

Danuta Owczarek ◽

Jacek Sapa ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Sensitivity And Specificity ◽

Activity Index ◽

Area Under The Curve ◽

Density Lipoprotein ◽

High Sensitivity ◽

Paraoxonase 1 ◽

Control Group ◽

Operating Characteristics

Diagnostics of Crohn’s disease (CD) requires noninvasive biomarkers facilitating early detection and differentiation of the disease. Therefore, in this study, we aimed to determine the relationship between paraoxonase-1 (PON-1), the severity of CD, oxidative stress, and inflammation in CD. The CD activity index was based on the current classification. Plasma PON-1 was measured in 47 patients with CD, and in 23 control volunteers. Using quantitative variables such as receiver operating characteristics (ROC) (area under the curve (AUC)), the diagnostic utility of PON-1 in differentiating the severity of CD was assessed. Circulating PON-1 was found to be decreased in the CD group compared to the control group (269.89 vs. 402.56 U/L, respectively), and it correlated well with the disease activity. PON-1 correlated positively with hemoglobin (Hb) (r = 0.539, p < 0.001), hematocrit (Ht) (r = 0.48, p < 0.001), total cholesterol (TC) (r = 0.343, p < 0.001), high density lipoprotein (HDL) (r = 0.536, p < 0.001), low density lipoprotein (LDL) (r = 0.54, p < 0.001), and triglyceride (TG) (r = 0.561, p < 0.001) and correlated negatively with white blood cell count (WBC) (r = −0.262, p = 0.029), platelet count (PLT) (r = −0.326, p = 0.006), C-reactive protein (CRP) (r = −0.61, p < 0.001), and malondialdehyde (MDA) (r = −0.924, p < 0.001). PON-1 as a marker for CD differentiation possessed a sensitivity and specificity of 93.62% and 91.30%, respectively. CD was found to be associated with the decrease in the levels of PON-1, which correlates well with activity of the disease and reflects the intensification of inflammation, as well as intensified lipid peroxidation. High sensitivity and specificity of PON-1 determines its selection as a good screening test for CD severity.

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Prostate-Specific antigen value and micro RNAs as potential diagnostic biomarkers for prostate cancer

Medical Science and Discovery ◽

10.36472/msd.v8i2.479 ◽

2021 ◽

Vol 8 (2) ◽

pp. 107-113

Author(s):

Aydemir Asdemir ◽

Sevgi Durna Dastan ◽

Esat Korgali ◽

Tugba Yildiz Asdemir ◽

Huseyin Saygin ◽

...

Keyword(s):

Prostate Cancer ◽

Specific Antigen ◽

Diagnostic Value ◽

Micro Rna ◽

Control Group ◽

Diagnostic Biomarkers ◽

Expression Levels ◽

Non Invasive ◽

Cancer Group ◽

Micro Rnas

Objective: It is necessary to provide PSA alternatives or methods that can be used in conjunction with PSA to regress complications rising from negative biopsies and to increase diagnostic value. Patients and Methods: The study is consisting of 59 men as the sample group. Blood samples from the individuals are grouped as prostate cancer and BPH (benign prostatic hyperplasia) groups. 27 prostate cancer patients whom some of them also operated are assembled in the patients group and the other 32 individuals are grouped as BPH group. Micro RNA expression levels evaluated by RT-PCR. Results: Prostate cancer group when compared with the control group, it is observed that expression levels of miRNA-221 and miRNA-432 increased while expression levels of miRNA-17-5p, miRNA-30c, miRNA-107, miRNA-141, miRNA-145, miRNA-181a-2, miRNA-331-3p, miRNA-574-3p decreased and expression levels of miRNA-21 and miRNA-375 are quite similar between the groups. Conclusion: The prospect of strong and sensitive serum miRNA expression levels in prostate cancer cases which are easily detectable by non-invasive methods as biomarkers is a promising field of study. Nevertheless, it is currently necessary to work in conjunction with both tissue and serum to enhance both sensitivity and specificity of miRNAs as biomarkers. As such, expression levels of the same miRNAs in tissue and serum provide different expression values which in turn make it difficult to indicate a common biomarker.

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

International Journal of Molecular Sciences ◽

10.3390/ijms20051154 ◽

2019 ◽

Vol 20 (5) ◽

pp. 1154 ◽

Cited By ~ 12

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.

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Urine Cell-Free DNA Integrity Analysis for Early Detection of Prostate Cancer Patients

Disease Markers ◽

10.1155/2015/574120 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 17

Author(s):

Samanta Salvi ◽

Giorgia Gurioli ◽

Filippo Martignano ◽

Flavia Foca ◽

Roberta Gunelli ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Specific Antigen ◽

Area Under The Curve ◽

Urogenital Tract ◽

Control Group ◽

Dna Integrity ◽

Characteristic Analysis ◽

Benign Diseases ◽

Lower Accuracy

Introduction. The detection of tumor-specific markers in urine has paved the way for new early noninvasive diagnostic approaches for prostate cancer. We evaluated the DNA integrity in urine supernatant to verify its capacity to discriminate between prostate cancer and benign diseases of the urogenital tract.Patients and Methods. A total of 131 individuals were enrolled: 67 prostate cancer patients and 64 patients with benign diseases of the urogenital tract (control group). Prostate-specific antigen (PSA) levels were determined. Urine cell-free (UCF) DNA was isolated and sequences longer than 250 bp corresponding to 3 genes (c-MYC,HER2, andAR) were quantified by Real-Time PCR to assess UCF-DNA integrity.Results. UCF-DNA was quantifiable in all samples, while UCF-DNA integrity was evaluable in all but 16 samples. Receiver operating characteristic analysis showed an area under the curve of 0.5048 for UCF-DNA integrity and 0.8423 for PSA. Sensitivity was 0.58 and 0.95 for UCF-DNA integrity and PSA, respectively. Specificity was 0.44 and 0.69, respectively.Conclusions. UCF-DNA integrity showed lower accuracy than PSA and would not seem to be a reliable marker for early prostate cancer diagnosis. Despite this, we believe that UCF-DNA could represent a source of other biomarkers and could detect gene alterations.

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Technetium-99m-MIBI-SPECT for prostate cancer diagnosis

Ukrainian Journal of Nephrology and Dialysis ◽

10.31450/ukrjnd.1(65).2020.04 ◽

2020 ◽

pp. 20-28

Author(s):

M. Kuru ◽

Z. Talat ◽

M. S. Sağer ◽

Ç. Demirdağ

Keyword(s):

Prostate Cancer ◽

Sensitivity And Specificity ◽

Cancer Diagnosis ◽

Prostate Biopsy ◽

Emission Computed Tomography ◽

Prostate Cancer Diagnosis ◽

Technetium 99M ◽

Non Invasive ◽

Invasive Method ◽

Mibi Spect

The gold standard method for prostate cancer diagnosis is a transrectal ultrasonography-guided prostate biopsy. The detection rate of prostate cancer using the biopsy is approximately 25-30%. A non-invasive method Technetium-99m methoxy-isobutyl-isonitrile single-photon emission computed tomography (technetium-99m-MIBI-SPECT) could be used in prostate cancer detected. The study aimed to try to show that Tc99m-MIBI-SPECT, which is performed as a non-invasive method before biopsy in patients with prostate biopsy indication, may prevent unnecessary biopsy among these patients. Methods. Fifty-six patients who were admitted to our clinic for any lower urinary tract symptoms or routine control and who had a digital rectal examination or PSA value indication for prostate biopsy were included in this retrospective study. Technetium-99m-MIBI-SPECT our patients before the biopsy was performed, radiopharmaceutical uptake by the intensity and localization of the prostate was detected. Technetium-99m-MIBI-SPECT localization and intensity of involvement by prostate biopsy results were evaluated by nuclear medicine specialists. Results. The patients’ age and PSA level were 62.8 (31-78) years and 11.3 (2.5-100) ng/ml, respectively. Prostate cancer was detected in 27/56 (48.2%) patients. The suspicious diagnosis in technetium-99m-MIBI-SPECT images was observed in 36/56 (64.3%) patients, but prostate cancer was detected in 20 of them only. The sensitivity and specificity of technetium-99m-MIBI-SPECT were 74% and 45%, respectively. The positive and negative predictive values were 55% and 45% respectively. The diagnostic value of technetium-99m-MIBI-SPECT methods was considered as 58%. Conclusıon: The technetium-99m-MIBI-SPECT method in this study had low sensitivity and specificity for prostate cancer diagnosis. Therefore, we came to the conclusion that technetium-99m-MIBI-SPECT cannot be an alternative diagnostic method.

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

Frontiers in Oncology ◽

10.3389/fonc.2020.610647 ◽

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.

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