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.

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

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.

scholarly journals Evaluation of Plasma Circulating Cell Free DNA Concentration and Integrity in Patients with Prostate Cancer in Jamaica: A Preliminary Study

Diseases ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 34
Author(s):  
Andrew Condappa ◽  
Donovan McGrowder ◽  
William Aiken ◽  
Wayne McLaughlin ◽  
Maxine Gossell-Williams
Keyword(s):  
Prostate Cancer ◽  
Gleason Score ◽  
Quantitative Polymerase Chain Reaction ◽  
Specific Antigen ◽  
Total Prostate Specific Antigen ◽  
Noninvasive Biomarker ◽  
Preliminary Study ◽  
Polymerase Chain ◽  
Free Circulating Dna ◽  
Total Psa

Background: Cell free circulating DNA (cfcDNA) is a promising diagnostic tool for prostate cancer (PCa). This study aimed to measure the cfcDNA concentration and integrity in PCa patients using quantitative polymerase chain reaction (qPCR) analysis. This study also assessed the correlation between these molecular biomarkers with total prostate-specific antigen (PSA), Gleason score, prostate volume, and age. Methods: Eleven PCa patients and 9 persons with benign prostatic hyperplasia (BPH) were recruited. Blood samples were collected before prostate biopsy and plasma quantified by qPCR amplification of the ALU 115 DNA sequence, with the ratio of ALU 247 to ALU 115 reflecting cfcDNA integrity. Results: There were no significant differences in median, interquartile range (IQR) cfcDNA concentration or cfcDNA integrity between the patients with PCa (47.9 (214.93) ng/mL; 0.61 (0.49)) and persons with BPH (41.5 (55.13) ng/mL, p = 0.382; 0.67 (0.45), p = 0.342). A weakly positive correlation exists between cfcDNA concentration and total PSA (r = 0.200, p = 0.555) but not with age or Gleason score in PCa patients. Conclusion: cfcDNA concentration was relatively nonsignificantly higher in PCa patients in comparison to persons with BPH, whereas cfcDNA integrity was similar in both groups. Though limited in sample size, this study shows that cfcDNA concentration may be a potentially valuable noninvasive biomarker for the diagnosis of PCa.

scholarly journals Catching the Sugars: Electrochemical Aptasensors for the Detection of Cancer-Related Glycosylation Changes in Prostate-Specific Antigen

Proceedings ◽  
2020 ◽  
Vol 60 (1) ◽  
pp. 47
Author(s):  
Ana Díaz-Fernández ◽  
Rebeca Miranda-Castro ◽  
Pedro Estrela ◽  
Noemí de-los-Santos-Álvarez ◽  
María Jesús Lobo-Castañón
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
False Positives ◽  
High Rate ◽  
Enzyme Linked Immunosorbent Assay ◽  
Glycan Structure ◽  
Specific Cancer ◽  
Different Levels ◽  
Selection Of

Prostate-specific Antigen (PSA) is the biomarker that is used for prostate cancer (PCa) detection, although its lack of specificity results in a high rate of false-positives and many unnecessary biopsies. Therefore, there is a need for more specific cancer biomarkers for PCa. Recent studies have shown that the aberrant glycosylation of proteins is a common feature of the presence of cancer. In the case of prostate cancer, there are changes in core-fucose and sialic acids in the glycan structure of PSA. In this work, we describe two different strategies to direct the selection of aptamers toward the glycans of PSA. From these strategies, we identified two aptamers (PSA-1 and PSAG-1) that bind to the glycan structure of PSA with high affinity. Both aptamers were applied in the design of electrochemical aptasensors, in sandwich and direct formats, in order to detect the changes in the glycosylation of PSA. The sensors responded to different levels of PSA in serum, and they showed higher potential to discriminate clinically-meaningful PCa than the ELISA (Enzyme-linked immunosorbent assay) test used in hospitals (reducing the number of false positives), although validation on more samples is needed.

scholarly journals The Combination of Human Glandular Kallikrein and Free Prostate-specific Antigen (PSA) Enhances Discrimination Between Prostate Cancer and Benign Prostatic Hyperplasia in Patients with Moderately Increased Total PSA

1999 ◽  
Vol 45 (11) ◽  
pp. 1960-1966 ◽  
Author(s):  
Angeliki Magklara ◽  
Andreas Scorilas ◽  
William J Catalona ◽  
Eleftherios P Diamandis
Keyword(s):  
Prostate Cancer ◽  
Benign Prostatic Hyperplasia ◽  
Prostate Specific Antigen ◽  
Prostatic Carcinoma ◽  
Specific Antigen ◽  
Area Under The Curve ◽  
Prostatic Hyperplasia ◽  
Free Psa ◽  
Glandular Kallikrein ◽  
Total Psa

Abstract Background: Prostate-specific antigen (PSA) is the most reliable tumor marker available and is widely used for the diagnosis and management of prostate cancer. Unfortunately, PSA cannot distinguish efficiently between benign and malignant disease of the prostate, especially within the range of 4–10 μg/L. Among the refinements developed to enhance PSA specificity is the free/total PSA ratio, which is useful in discriminating between the two diseases within the diagnostic “gray zone”. Recent data indicate that human glandular kallikrein (hK2), a protein with high homology to PSA, may be an additional serum marker for the diagnosis and monitoring of prostate cancer. Methods: We analyzed 206 serum samples (all before treatment was initiated) from men with histologically confirmed benign prostatic hyperplasia (n = 100) or prostatic carcinoma (n = 106) with total PSA in the range of 2.5–10 μg/L. Total and free PSA and hK2 were measured with noncompetitive immunological procedures. Statistical analysis was performed to investigate the potential utility of the various markers or their combinations in discriminating between benign prostatic hyperplasia and prostatic carcinoma. Results: hK2 concentrations were not statistically different between the two groups of patients. There was a strong positive correlation between hK2 and free PSA in the whole patient population. hK2/free PSA ratio (area under the curve = 0.69) was stronger predictor of prostate cancer than the free/total PSA ratio (area under the curve = 0.64). At 95% specificity, the hK2/free PSA ratio identified 30% of patients with total PSA between 2.5–10 μg/L who had cancer. At 95% specificity, the hK2/free PSA ratio identified 25% of patients with total PSA between 2.5 and 4.5 μg/L who had cancer. Conclusions: Our data suggest that hK2 in combination with free and total PSA can enhance the biochemical detection of prostate cancer in patients with moderately increased total PSA concentrations. More specifically, the hK2/free PSA ratio appears to be valuable in identifying a subset of patients with total PSA between 2.5 and 4.5 μg/L who have high probability of cancer and who should be considered for biopsy.

Paclitaxel, Estramustine Phosphate, and Carboplatin in Patients With Advanced Prostate Cancer

2001 ◽  
Vol 19 (1) ◽  
pp. 44-53 ◽  
Author(s):  
William Kevin Kelly ◽  
Tracy Curley ◽  
Susan Slovin ◽  
Glenn Heller ◽  
John McCaffrey ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Specific Antigen ◽  
Area Under The Curve ◽  
Complete Response ◽  
Dose Escalation Study ◽  
Time Curve ◽  
Grade 3 ◽  
Safe Dose ◽  
Androgen Independent

PURPOSE: To determine the safety and activity of weekly paclitaxel in combination with estramustine and carboplatin (TEC) in patients with advanced prostate cancer. PATIENTS AND METHODS: In a dose-escalation study, patients with advanced prostate cancer were administered paclitaxel (weekly 1-hour infusions of 60 to 100 mg/m2), oral estramustine (10 mg/kg), and carboplatin (area under the curve, 6 mg/mL-min every 4 weeks). Paclitaxel levels were determined 0, 30, 60, 90, and 120 minutes and 18 hours after infusion, and a concentration-time curve was estimated. Once a safe dose was established, a multi-institutional phase II trial was conducted in patients with progressive androgen-independent disease. RESULTS: Fifty-six patients with progressive androgen-independent disease were treated for a median of four cycles. The dose of paclitaxel was escalated from 60 to 100 mg/m2 without the occurrence of DLT. Posttherapy decreases in serum prostate-specific antigen levels of 50%, 80%, and 90% were seen in 67%, 48%, and 39% (95% confidence interval, 55% to 79%, 35% to 61%, 26% to 52%) of the patients, respectively. Of the 33 patients with measurable disease, two (6%) had a complete response and 13 (39%) had a partial response. The overall median time to progression was 21 weeks, and the median survival time for all patients was 19.9 months. Major grade 3 or 4 adverse effects were thromboembolic disease (in 25% of patients), hyperglycemia (in 38%), and hypophosphatemia (in 42%). Significant leukopenia, thrombocytopenia, and peripheral neuropathy were not observed. CONCLUSION: TEC has significant antitumor activity and is well tolerated in patients with progressive androgen-independent prostate cancer.

scholarly journals Independent Validation of a Diagnostic Noninvasive 3-MicroRNA Ratio Model (uCaP) for Prostate Cancer in Cell-Free Urine

2019 ◽  
Vol 65 (4) ◽  
pp. 540-548 ◽  
Author(s):  
Jacob Fredsøe ◽  
Anne K I Rasmussen ◽  
Emma B Laursen ◽  
Yunpeng Cai ◽  
Kenneth A Howard ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Biopsy ◽  
Specific Antigen ◽  
Transrectal Ultrasound ◽  
Area Under The Curve ◽  
Extracellular Vesicle ◽  
Urine Samples ◽  
Ratio Model ◽  
Psa Testing ◽  
Diagnostic Potential

Abstract BACKGROUND Detection of prostate cancer (PC) based on serum prostate-specific antigen (PSA) testing leads to many unnecessary prostate biopsies, overdiagnosis, and overtreatment of clinically insignificant tumors. Thus, novel and more accurate molecular biomarkers are required. METHODS Using reverse transcription quantitative PCR, we measured the concentrations of 45 preselected microRNAs (miRNAs) in extracellular vesicle-enriched cell-free urine samples from 4 independent patient cohorts from Spain and Denmark, including 758 patients with clinically localized PC, 289 noncancer controls with benign prostatic hyperplasia (BPH), and 233 patients undergoing initial transrectal ultrasound (TRUS)-guided prostate biopsy owing to PC suspicion (101 with benign and 132 with malignant outcome). Diagnostic potential was assessed by ROC and decision curve analysis. RESULTS We identified and successfully validated 8 upregulated and 21 downregulated miRNAs in urine from PC patients. Furthermore, we validated a previously identified 3-miRNA diagnostic ratio model, uCaP (miR-222–3p*miR-24–3p/miR-30c-5p). High uCaP scores were distinctive of PC in urine samples from BPH vs PC patients in 3 independent cohorts [area under the curve (AUC) = 0.84, 0.71, 0.72]. Additionally, uCaP predicted TRUS biopsy results with greater accuracy than PSA (AUC uCaP = 0.644; AUC PSA = 0.527) for patients within the diagnostic gray zone (PSA ≤ 10 ng/mL). CONCLUSIONS We successfully validated a urine-based diagnostic 3-miRNA signature for PC (uCaP) in 3 independent patient cohorts from 2 countries. In the future, the simple and noninvasive uCaP test may be used to help more accurately select patients for prostate biopsy. Prospective clinical validation is warranted.

A urine exosomal circRNA classifier for detection of high-grade prostate cancer at initial biopsy: A multicenter, retrospective study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5522-5522
Author(s):  
Liaoyuan Li ◽  
Wen Tao ◽  
Yadi He ◽  
Tao He ◽  
Qing Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Validation Cohort ◽  
Characteristic Curve ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
Circular Rna ◽  
High Grade ◽  
Training Cohort ◽  
Potential Biomarker ◽  
Initial Biopsy

5522 Background: The low specificity of prostate-specific antigen (PSA) has resulted in the overdiagnosis and overtreatment of clinically indolent prostate cancer (PCa). We aimed to identify a urine exosomal circular RNA (circRNA) classifier that could detect high-grade (Gleason score [GS]7 or greater) PCa. Methods: We did a three-stage study that enrolled eligible participants, including PCa-free men, 45 years or older, scheduled for an initial prostate biopsy due to suspicious digital rectal examination findings and/or PSA levels (limit range, 2.0-20.0 ng/mL), from four hospitals in China. We used RNA sequencing and digital droplet polymerase chain reaction to identify 18 candidate urine exosomal circRNAs that were increased in 11 patients with high-grade PCa compared with 11 case-matched patients with benign prostatic hyperplasia. Using a training cohort of eligible participants, we built a urine exosomal circRNA classifier (Ccirc) to detect high-grade PCa. We then evaluated the classifier in discrimination of GS7 or greater from GS6 and benign disease on initial biopsy in two independent cohorts. We used the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) to evaluate diagnostic performance, and compared Ccirc with standard of care (SOC) (ie, PSA level, age, race, and family history). Results: Between June 1, 2016, and July 31, 2019, we recruited 356 participants to the training cohort, and 442 and 325 participants to the two independent validation cohorts. We identified a Ccirc containing five differentially expressed circRNAs (circ_0049335, circ_0056536, circ_0004028, circ_0008475, and circ_0126027) that could detect high-grade PCa. Ccirc showed higher accuracy than SOC to distinguish individuals with high-grade PCa from controls in both the training cohort and the validation cohorts. (AUC 0.831 [95% CI 0.765-0.883] vs 0.724 [0.705-0.852], P = 0.032 in the training cohort; 0.823 [0.762-0.871] vs 0.706 [0.649-0.762], P = 0.007 in validation cohort 1; and 0.878 [0.802-0.943] vs 0.785 [0.701-0.890], P = 0.021 for validation cohort 2). In all three cohorts, Ccirc had higher sensitivity (range 71.6-87.2%) and specificity (82.3-90.7%) than did SOC (sensitivity, 42.3-68.2%; specificity, 40.1-62.3%) to detect high-grade PCa. Using a predefined cut point, 202 of 767 (26.3%) biopsies would have been avoided, missing only 6% of patients with dominant pattern 4 high-risk GS 7 disease. Conclusions: Ccirc is a potential biomarker for high-grade PCa among suspicious men.

scholarly journals APTIMA PCA3 Molecular Urine Test: Development of a Method to Aid in the Diagnosis of Prostate Cancer

2006 ◽  
Vol 52 (6) ◽  
pp. 1089-1095 ◽  
Author(s):  
Jack Groskopf ◽  
Sheila MJ Aubin ◽  
Ina Lim Deras ◽  
Amy Blase ◽  
Sharon Bodrug ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Biopsy ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
Prostate Cancer Risk ◽  
Area Under The Curve ◽  
Roc Curve Analysis ◽  
Cancer Risk Factors ◽  
Specimen Processing ◽  
Whole Urine

Abstract Background: Prostate cancer gene 3 (PCA3) encodes a prostate-specific mRNA that has shown promise as a prostate cancer diagnostic tool. This report describes the characterization of a prototype quantitative PCA3-based test for whole urine. Methods: Whole-urine specimens were collected after digital rectal examination from 3 groups: men scheduled for prostate biopsy (n = 70), healthy men (<45 years of age with no known prostate cancer risk factors; n = 52), and men who had undergone radical prostatectomy (n = 21). PCA3 and prostate-specific antigen (PSA) mRNAs were isolated, amplified, and quantified by use of Gen-Probe DTS400® Systems. Prostate biopsy results were correlated with the PCA3/PSA mRNA ratio, and PSA mRNA concentrations were used to normalize PCA3 signals and confirm the yield of prostate-specific RNA. Assay precision, specimen stability, and mRNA yield were also evaluated. Results: The specimen informative rate (fraction of specimens yielding sufficient RNA for analysis) was 98.2%. In this clinical research study, ROC curve analysis of prebiopsy specimens yielded an area under the curve of 0.746; sensitivity was 69% and specificity 79%. Serum PSA assay specificity was 28% for this same group. PCA3 and PSA mRNAs were undetectable in postprostatectomy specimens except for one man with recurrent prostate cancer. Assay interrun CVs were ≤12%. Both mRNAs were stable in processed urine up to 5 days at 4 °C and after 5 freeze–thaw cycles. Conclusion: The APTIMA® PCA3 assay combines simple specimen processing with precise assays and existing instruments and could add specificity to the current algorithm for prostate cancer diagnosis.

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