Different free prostate-specific antigen to total prostate-specific antigen ratios using three detecting systems.
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ABSTRACT:
SUBMITTER: Huang HQ
PROVIDER: S-EPMC6817054 | biostudies-literature | 2018 Feb
REPOSITORIES: biostudies-literature
Publications
Different free prostate-specific antigen to total prostate-specific antigen ratios using three detecting systems.
Huang Hui-Qing HQ Zhang Yan Y Xu Hua-Guo HG
Journal of clinical laboratory analysis 20170406 2
<h4>Background</h4>Prostate-specific antigen (PSA) is used as an indicative marker of a pathologic condition of the prostate, and the ratio of free PSA (fPSA) to total PSA (tPSA) helps to distinguish benign prostatic hyperplasia (BPH) from prostate cancer (PCa). In this study, we present some reversed ratios of fPSA to tPSA and analyze the possible mechanism.<h4>Methods</h4>Using the UniCel DxI800 Access Immunoassay System, eight reversed fPSA to tPSA ratios were obtained, and then these samples ...[more]
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Project description:BackgroundScreening for prostate cancer using prostate-specific antigen (PSA) is common. Prostate cancer has been associated with higher total PSA (tPSA), lower free PSA (fPSA), lower percent free PSA (%fPSA), and higher complexed PSA (cPSA).MethodsTotal, free and complexed PSAs were performed on 3251 men ≥40years in the 2007-2010 National Health and Nutrition Examination Survey. Distributions of the PSA tests were examined by age, race and ethnicity, and body mass index (BMI) groups. Percentages of men at PSA thresholds were examined.ResultsTotal PSA geometric mean was 0.96μg/l among men aged ≥40years and increased from 0.74μg/l for men 40-49years, to 1.82μg/l for men 80years and older. Non-Hispanic Whites had lower age-adjusted mean tPSA (1.03μg/l) and cPSA (0.56μg/l) than non-Hispanic Blacks (tPSA 1.25μg/l and cPSA 0.72μg/l). Obese men had lower age-adjusted mean total, free and complexed PSAs (0.94, 0.27, and 0.51μg/l, respectively) than men with normal BMI (tPSA 1.21, fPSA 0.32, and cPSA 0.68μg/l, respectively).ConclusionTotal, free and complexed PSAs increased with age; tPSA and cPSAs were highest in non-Hispanic Blacks; and total, free, and complexed PSAs were lowest in obese men.
| S-EPMC7456738 | biostudies-literature
Project description:Background The lack of interchangeability among prostate-specific antigen (PSA) assays causes difficulties in clinical interpretation. The currently available mainstream assays for PSA were based on Western populations, but it is not clear whether these assays yield different results in prostate cancer (PCa) screening in Chinese populations. Methods A total of 163 men with a total PSA (tPSA) level of 2–10 µg/L scheduled for prostate biopsy were enrolled in this study. The levels of the tPSA and free PSA (fPSA) were detected by the Beckman (using the Hybritech calibration), Roche, Abbott, and Mindray (using the World Health Organization’s calibration). Methodological comparison were performed according to EP9-A3 of the Clinical and Laboratory Standards Institute, USA. With pathological diagnosis as the gold standard, the predictive accuracy of the biomarkers was quantified as the area under the receiver operating characteristic curve (AUC) for each of the four methods. Results A total of 32 PCa patients and 131 patients with benign prostate disease were included in this study. The tPSA levels detected by the Roche, Abbott, and Mindray showed good consistency with Beckman but not of the fPSA levels. Compared to the Beckman tPSA values, the measured values were 1.1% higher for Roche, 2.1% higher for Abbott, and 6.7% higher for Mindray. The fPSA levels measured by Roche, Abbott, and Mindray were 5.4% lower, 22.1% higher, and 4.6% higher than Beckman, respectively. When the tPSA was 4 ng/mL, the diagnostic performance (sensitivity, specificity, positive predictive value, negative predictive value, and missed diagnosis rate) was similar among these 4 assays. When the %fPSA was 16%, Abbott had the highest missed diagnosis rate (37.50%), while Mindray had a sensitivity of 81.25%, the highest negative predictive value (93.88%), and the lowest missed diagnosis rate (18.75%). Conclusions When the tPSA level is 2–10 ng/mL, the Mindray, like the Roche and Abbott, has good consistency with the Beckman in detecting tPSA, which makes it possible to relieve the pressure of clinical interpretation. However, 4 assays using the same %fPSA cut-off may lead to diverse missed diagnosis rates for PCa screening in China.
| S-EPMC10006006 | biostudies-literature
Project description:Late-stage prostate cancer often acquires resistance to conventional chemotherapies and transforms into a hormone-refractory, drug-resistant, and non-curative disease. Developing non-invasive tools to detect the biochemical changes that correlate with drug efficacy and reveal the onset of drug resistance would have important ramifications in managing the treatment regimen for individual patients. Here, we report the selection of new Designed Ankyrin Repeat Proteins (DARPins) that show high affinity toward prostate-specific antigen (PSA), a biomarker used in clinical monitoring of prostate cancer. Ribosome display and in vitro screening tools were used to select PSA-binding DARPins based on their binding affinity, selectivity, and chemical constitution. Surface plasmon resonance measurements demonstrated that the four lead candidates bind to PSA with nanomolar affinity. DARPins were site-specifically functionalised at a unique C-terminal cysteine with a hexadentate aza-nonamacrocyclic chelate (NODAGA) for subsequent radiolabelling with the positron-emitting radionuclide 68Ga. [68Ga]GaNODAGA-DARPins showed high stability toward transchelation and were stable in human serum for >2 h. Radioactive binding assays using streptavidin-loaded magnetic beads confirmed that the functionalisation and radiolabelling did not compromise the specificity of [68Ga]GaNODAGA-DARPins toward PSA. Biodistribution experiments in athymic nude mice bearing subcutaneous prostate cancer xenografts derived from the LNCaP cell line revealed that three of the four [68Ga]GaNODAGA-DARPins displayed specific tumour-binding in vivo. For DARPin-6, tumour-uptake in the normal group reached 4.16 ± 0.58% ID g-1 (n = 3; 2 h post-administration) and was reduced by ∼50% by competitive binding with a low molar activity formulation (blocking group: 2.47 ± 0.42% ID g-1; n = 3; P value = 0.018). Collectively, the experimental results support the future development of new PSA-specific imaging agents for potential use in monitoring the efficacy of androgen receptor (AR)-targeted therapies.
| S-EPMC10320840 | biostudies-literature
Project description:Percent free prostatic-specific antigen (%fPSA) has been introduced as a tool to avoid unnecessary biopsies in patients with a serum PSA level of 4.0-10.0 ng ml-1 , however, it remains controversial whether %fPSA is effective in PSA range of 10.1-20.0 ng ml-1 in both Chinese and Western population. In this study, the diagnostic performance of %fPSA and serum PSA in predicting prostate cancer (PCa) and high-grade PCa (HGPCa) was analyzed in a multi-center biopsy cohort of 5915 consecutive Chinese patients who underwent prostate biopsy in 22 hospitals across China from January 1, 2010 to December 31, 2013. The indication for biopsy was PSA>4.0 ng ml-1 or/and suspicious digital rectal examination. Total and free serum PSA determinations were performed by three types of electrochemiluminescence immunoassays with recalibration to the World Health Organization standards. The diagnostics accuracy of PSA, %fPSA and %fPSA in combination with PSA (%fPSA + PSA) was determined by the area under the receivers operating characteristic curve (AUC). %fPSA was more effective than PSA in men aged ≥60 years old. The AUC was 0.584 and 0.635 in men aged ≥60 years old with a PSA of 4.0-10.0 ng ml-1 and 10.1-20.0 ng ml-1 , respectively. The AUC of %fPSA was superior to that of PSA in predicting HGPCa in patients ≥60 years old in these two PSA range. Our results indicated that %fPSA is both statistically effective and clinical applicable to predict prostate biopsy outcome in Chinese patients aged ≥60 years old with a PSA of 4.0-10.0 ng ml-1 and 10.1-20.0 ng ml-1 .
| S-EPMC4814972 | biostudies-literature
Project description:Despite intense efforts to develop radiotracers to detect cancers or monitor treatment response, few are widely used as a result of challenges with demonstrating clear clinical use. We reasoned that a radiotracer targeting a validated clinical biomarker could more clearly assess the advantages of imaging cancer. The virtues and shortcomings of measuring secreted prostate-specific antigen (PSA), an androgen receptor (AR) target gene, in patients with prostate cancer are well documented, making it a logical candidate for assessing whether a radiotracer can reveal new (and useful) information beyond that conferred by serum PSA. Therefore, we developed (89)Zr-labeled 5A10, a novel radiotracer that targets "free" PSA. (89)Zr-5A10 localizes in an AR-dependent manner in vivo to models of castration-resistant prostate cancer, a disease state in which serum PSA may not reflect clinical outcomes. Finally, we demonstrate that (89)Zr-5A10 can detect osseous prostate cancer lesions, a context where bone scans fail to discriminate malignant and nonmalignant signals.This report establishes that AR-dependent changes in PSA expression levels can be quantitatively measured at tumor lesions using a radiotracer that can be rapidly translated for human application and advances a new paradigm for radiotracer development that may more clearly highlight the unique virtues of an imaging biomarker.
| S-EPMC3351274 | biostudies-literature
Project description:Background and objectiveProstate-specific antigen (PSA) remains a critical marker for prostate cancer (PCa) detection and monitoring. Recognising historical variability in PSA assays and the evolution of assay technology and calibration, this study aims to reassess interassay variability using the latest generation of five assays in a contemporary cohort of men undergoing prostate biopsy.MethodsFive different commercially available PSA assays were tested in a blood sample of 76 men before undergoing a prostate biopsy. Total PSA (tPSA) and free-to-total PSA ratio (%fPSA) were compared across assays, using Roche (Basel, Switzerland) as the benchmark, and correlated with biopsy outcome to analyse the impact on PCa diagnosis. The statistical analysis included Passing-Bablok regression and Bland-Altman plots, with a p value threshold of <0.05 for significance.Key findings and limitationsAmong the 76 men, 28 (36.8%) were diagnosed with significant PCa (defined as International Society of Urological Pathology grade ≥2). A high correlation was observed between tPSA and %fPSA values among the different PSA assays tested (r2 ≥ 0.9). The Passing-Bablok analysis showed that tPSA results varied substantially among the assays, with slopes ranging between 0.78 and 1.04. Compared with the tPSA of Roche, tPSA values were on average 20.7% lower by Beckman (Oststeinbeck, Germany), 15.2% lower by Abbott (Chicago, IL, USA), 6.1% lower by Diasorin (Saluggia, Italy), and 9.6% higher by Brahms (Hennigsdorf, Germany; p < 0.001 for all). The %fPSA values by Abbott and Brahms were higher at 15.7% and 10.6%, respectively (p < 0.001), while the Beckman and Diasorin values had minimal differences of -0.3% and 2.3%, respectively (p > 0.05). The variability across assays would have resulted in discrepancies in both the sensitivity and the specificity for tPSA and %fPSA by at least 14%, depending on the cut-offs applied.Conclusions and clinical implicationsDespite the use of the latest PSA assays, relevant variability of tPSA and %fPSA results can be observed among different assays. There is an urgent need for standardised calibration methods and greater awareness among practitioners concerning interassay variability. Clinicians should acknowledge that clinically relevant thresholds may depend on the specific PSA assay and that ideally the same assay is applied over time for better clinical decision-making.Patient summaryProstate-specific antigen (PSA) is a critical marker for prostate cancer (PCa) detection and monitoring. However, significant variations were observed in the results of the latest PSA assays. Thus, standardised calibration methods and greater awareness among practitioners concerning interassay variability are needed.
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Project description:In recent decades, it has become clear that most of human proteins are glycosylated and that protein glycosylation plays an important role in health and diseases. At present, simple, fast and inexpensive methods are sought for clinical applications and particularly for improved diagnostics of various diseases, including cancer. We propose a label- and reagent-free electrochemical method based on chronopotentiometric stripping (CPS) analysis and a hanging mercury drop electrode for the detection of interaction of sialylated protein biomarker a prostate specific antigen (PSA) with two important lectins: Sambucus nigra agglutinin (SNA) and Maackia amurensis agglutinin (MAA). Incubation of PSA-modified electrode with specific SNA lectin resulted in an increase of CPS peak H of the complex as compared to this peak of individual PSA. By adjusting polarization current and temperature, PSA-MAA interaction can be either eliminated or distinguished from the more abundant PSA-SNA complex. CPS data were in a good agreement with the data obtained by complementary methods, namely surface plasmon resonance and fluorescent lectin microarray. It can be anticipated that CPS will find application in glycomics and proteomics.
| S-EPMC5667740 | biostudies-literature
Project description:BackgroundProstate-specific antigen (PSA) testing has limited accuracy for the early detection of prostate cancer (PCa).ObjectiveTo assess the value added by percentage of free to total PSA (%fPSA), prostate cancer antigen 3 (PCA3), and a kallikrein panel (4k-panel) to the European Randomised Study of Screening for Prostate Cancer (ERSPC) multivariable prediction models: risk calculator (RC) 4, including transrectal ultrasound, and RC 4 plus digital rectal examination (4+DRE) for prescreened men.Design, setting, and participantsParticipants were invited for rescreening between October 2007 and February 2009 within the Dutch part of the ERSPC study. Biopsies were taken in men with a PSA level ≥3.0 ng/ml or a PCA3 score ≥10. Additional analyses of the 4k-panel were done on serum samples.Outcome measurements and statistical analysisOutcome was defined as PCa detectable by sextant biopsy. Receiver operating characteristic curve and decision curve analyses were performed to compare the predictive capabilities of %fPSA, PCA3, 4k-panel, the ERSPC RCs, and their combinations in logistic regression models.Results and limitationsPCa was detected in 119 of 708 men. The %fPSA did not perform better univariately or added to the RCs compared with the RCs alone. In 202 men with an elevated PSA, the 4k-panel discriminated better than PCA3 when modelled univariately (area under the curve [AUC]: 0.78 vs. 0.62; p=0.01). The multivariable models with PCA3 or the 4k-panel were equivalent (AUC: 0.80 for RC 4+DRE). In the total population, PCA3 discriminated better than the 4k-panel (univariate AUC: 0.63 vs. 0.56; p=0.05). There was no statistically significant difference between the multivariable model with PCA3 (AUC: 0.73) versus the model with the 4k-panel (AUC: 0.71; p=0.18). The multivariable model with PCA3 performed better than the reference model (0.73 vs. 0.70; p=0.02). Decision curves confirmed these patterns, although numbers were small.ConclusionsBoth PCA3 and, to a lesser extent, a 4k-panel have added value to the DRE-based ERSPC RC in detecting PCa in prescreened men.Patient summaryWe studied the added value of novel biomarkers to previously developed risk prediction models for prostate cancer. We found that inclusion of these biomarkers resulted in an increase in predictive ability.
| S-EPMC4407822 | biostudies-literature
Project description:We aimed to determine whether vitamin D levels before prostate biopsy have diagnostic value for clinically significant prostate cancer. The study cohort included patients who underwent prostate biopsy. A total of 224 patients were enrolled in our study and serum vitamin D levels were measured from February 2016 to December 2019 in routine laboratory tests. To determine the relationship between vitamin D levels and aggressiveness of prostate cancer, we used logistic multivariate analysis. Based on the histopathological results of patients who underwent radical prostatectomy, the serum vitamin D level was significantly lower with the large tumor volume group. In the univariate analysis, the prostate cancer diagnosis rate was associated with low vitamin D levels. Low vitamin D level is negatively correlated with clinically significant prostate cancer (biopsy Gleason score of 7 or higher) in the univariate (Odds ratio [OR], 0.955; P < 0.001) and multivariate (OR, 0.944; P = 0.027) analyses. In conclusion, we found that the incidence of clinically significant prostate cancer might related to low vitamin D level in the Asian population. In the future, a larger population and prospective study are needed.
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Project description:Prostate cancer (PC) is the most common noncutaneous malignancy affecting men in the US, leading to significant morbidity and mortality. While significant therapeutic advances have been made, available systemic therapeutic options are lacking. Prostate-specific membrane antigen (PSMA) is a highly-restricted prostate cell-surface antigen that may be targeted. While initial anti-PSMA monoclonal antibodies were suboptimal, the development of monoclonal antibodies such as J591 which are highly specific for the external domain of PSMA has allowed targeting of viable, intact prostate cancer cells. Radiolabeled J591 has demonstrated accurate and selective tumor targeting, safety, and efficacy. Ongoing studies using anti-PSMA radioimmunotherapy with (177)Lu-J591 seek to improve the therapeutic profile, select optimal candidates with biomarkers, combine with chemotherapy, and prevent or delay the onset of metastatic disease for men with biochemical relapse. Anti-PSMA monoclonal antibody-drug conjugates have also been developed with completed and ongoing early-phase clinical trials. As PSMA is a selective antigen that is highly overexpressed in prostate cancer, anti-PSMA-based immunotherapy has also been studied and utilized in clinical trials.
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