Prostate-specific Antigen/Solvent Interaction Analysis: A Preliminary Evaluation of a New Assay Concept for Detecting Prostate Cancer Using Urinary Samples

Abstract

Objectives To provide preliminary clinical performance evaluation of a novel CaP assay, PSA/SIA (Solvent Interaction Analysis) that focused on changes to the structure of PSA. Methods 222 men undergoing prostate biopsy for accepted clinical criteria at three sites (University Hospitals Case Medical Center in Cleveland, Cleveland Clinic, and Veterans Administration Boston Healthcare System) were enrolled in IRB approved study. Prior to TRUS guided biopsy, patients received DRE with systematic prostate massage followed by collection of urine. The PSA/SIA assay determined the relative partitioning of heterogeneous PSA isoform populations in urine between two aqueous phases. A structural index, K, whose numerical value is defined as the ratio of the concentration of all PSA isoforms, was determined by total PSA ELISA and used to set a diagnostic threshold for CaP. Performance was assessed using ROC analysis with biopsy as the gold standard. Results Biopsies were pathologically classified as case (malignant, n=100) or control (benign, n=122). ROC performance demonstrated AUC=0.90 for PSA/SIA and 0.58 for serum tPSA. At a cutoff value of K=1.73, PSA/SIA displayed sensitivity=100%, specificity=80.3%, PPV=80.6%, and NPV=100%. No attempt was made in this preliminary study to further control patient population or selection criteria for biopsy, nor did we analytically investigate the type of structural differences in PSA that led to changes in K value. Conclusions PSA/SIA provides ratiometric information independently of PSA concentration. In this preliminary study, analysis of the overall structurally heterogeneous PSA isoform population using the SIA assay showed promising results to be further evaluated in future studies.

Towards the differential diagnosis of prostate cancer by the pre-treatment of human urine using ionic liquids

“…Based on these results, adequate IL-based ABS can be used to effectively pre-treat human urine samples, leading to the concentration and quantification of more than one form of PSA while paving the way to PCa differential cancer diagnosis and monitoring. The approach here proposed www.nature.com/scientificreports/ is different from that reported in previous studies dealing with ABS composed of two polymers [14][15][16] . Instead of analysing the partition behaviour of PSA and respective isoforms, and where the partition coefficient is directly used in diagnosis, in this work IL-based ABS are used as pre-treatment strategies of biological samples, allowing the quantification of cancer biomarkers by SE-HPLC and not by immunoassays as usually carried out [14][15][16] .…”

“…Previous works reported on the use of ABS composed of two polymers, namely dextran and ficoll, to extract PSA 14 ; nevertheless, these systems do not allow the complete extraction and concentration of PSA in one phase. Accordingly, subsequent studies 15,16 focused on the quantification of PSA isoforms and determination of their partition coefficients between the ABS coexisting phases. Overall, in all studies reported so far, it was not possible to completely extract PSA to a given phase, thus preventing the use of ABS in pre-treatment strategies of human fluids as proposed in the current work.…”

“…Overall, in all studies reported so far, it was not possible to completely extract PSA to a given phase, thus preventing the use of ABS in pre-treatment strategies of human fluids as proposed in the current work. Furthermore, due to the low amounts of the target biomarker, the quantification of PSA in these works 15,16 was performed by immunoassays, an expensive technique often unavailable in developing countries.…”

Origin of salt additive effect on solute partitioning in aqueous polyethylene glycol-8000–sodium sulfate two-phase system

“…Therefore they can be used for the discriminating distribution of added solutes. ATPSs have been used for separation of biological macromolecules and particles for over 50 years [5][6][7] and recently found use in a variety of analytical applications as well [8,9].…”

Evaluation of Knowledge of Medical Students of University of Lomé (Togo) on the Contribution of Prostate Biopsy in the Detection of Prostate Cancer

“…The constant decrease in specific mortality from prostate cancer observed in recent years in the USA and France through data from cancer registers, partly responds to the interest in individual screening for men aged 50 to 75 with a long life expectancy greater than 10 years [3] [4]. The diagnosis of prostate cancer is established by prostate biopsy and allows a real mapping of the prostate to be carried out [5] [6]. Many prostate cancers are detected based on high plasma levels of prostate specific antigen (PSA > 4 ng/mL), a glycoprotein normally expressed by prostate tissue [6].…”