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Cancer Feb 2018
Topics: Aged; Early Detection of Cancer; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms
PubMed: 29231972
DOI: 10.1002/cncr.31140 -
Journal of Proteomics Apr 2021Early detection of prostate cancer may lead to the overdiagnosis and overtreatment of patients as well as missing significant cancers. The current diagnostic approach...
Early detection of prostate cancer may lead to the overdiagnosis and overtreatment of patients as well as missing significant cancers. The current diagnostic approach uses elevated serum concentrations of prostate-specific antigen (PSA) as an indicator of risk. However, this test has been widely criticized as it shows poor specificity and sensitivity. In order to improve early detection and diagnosis, several studies have investigated whether different PSA proteoforms are correlated to prostate cancer. Until now, studies and methodologies for the comprehensive characterization of PSA proteoforms from biofluids are scarce. For this purpose, we developed an intact protein assay to analyze PSA by capillary electrophoresis-electrospray ionization-mass spectrometry after affinity purification from patients' urine. Here, we determined six proteolytic cleavage variants. In regard to glycosylation, tri-, di-, mono- and non-sialylated complex-type N-glycans were found on non-cleaved PSA, as well as the non-glycosylated variant. The performance of the intact protein assay was assessed using a pooled sample, obtaining an inter-day variability of 15%. Furthermore, urinary patient samples were analyzed by intact protein analysis and a bottom-up approach (glycopeptide analysis). This combined approach revealed complimentary information on both levels, demonstrating the benefit of using two orthogonal techniques to provide a thorough profile of urinary PSA. SIGNIFICANCE: The detection of clinically relevant prostate cancer requires a more specific and sensitive biomarker and, in this case, several PSA proteoforms may be able to aid or improve the current PSA test. However, a comprehensive analysis of the intact PSA proteoform profile is still lacking. This study investigated the PSA proteoforms present in urine and, in particular, determined the relative contribution of cleaved PSA and non-cleaved PSA forms to the total glycosylation profile. Importantly, intact protein analysis did not require further sample treatment before being measured by CE-ESI-MS. Furthermore, its glycosylation was also assessed in a bottom-up approach to provide complementary information. Overall, these results represent an important basis for future characterization and biomarker studies.
Topics: Electrophoresis, Capillary; Glycopeptides; Glycosylation; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms
PubMed: 33618028
DOI: 10.1016/j.jprot.2021.104148 -
Prostate Cancer and Prostatic Diseases Apr 2018Screening for prostate cancer using prostate-specific antigen (PSA) alone leads to un-necessary biopsying and overdiagnosis. PSA density is easily accessible, but early...
BACKGROUND
Screening for prostate cancer using prostate-specific antigen (PSA) alone leads to un-necessary biopsying and overdiagnosis. PSA density is easily accessible, but early evidence on its use for biopsy decisions was conflicting and use of PSA density is not commonly recommended in guidelines.
METHODS
We analyzed biopsy outcomes in 5291 men in the population-based STHLM3 study with PSA ≥ 3 ng/ml and ultrasound-guided prostate volume measurements by using percentages and regression models. PSA density was calculated as total PSA (ng/ml) divided by prostate volume (ml). Main endpoint was clinically significant cancer (csPCa) defined as Gleason Score ≥ 7.
RESULTS
The median PSA-density was 0.10 ng/ml (IQR 0.075-0.14). PSA-density was associated with the risk of finding csPCa both with and without adjusting for the additional clinical information age, family history, previous biopsies, total PSA and free/total PSA (OR 1.06; 95% CI:1.05-1.07 and OR 1.07, 95% CI 1.06-1.08). Discrimination for csPCa was better when PSA density was added to a model with additional clinical information (AUC 0.75 vs. 0.73, P < 0.05). The proportion of men with Gleason Score 6 (ISUP 1) was similar across stratas of PSA-density. Omitting prostate biopsy for men with PSA-density ≤0.07 ng/ml would save 19.7% of biopsy procedures, while missing 6.9% of csPCa. PSA-density cutoffs of 0.10 ng/ml and 0.15 ng/ml resulted in detection of 77% (729/947) and 49% (461/947) of Gleason Score ≥7 tumors.
CONCLUSIONS
PSA-density might inform biopsy decisions, and spare some men from the morbidity associated with a prostate biopsy and diagnosis of low-grade prostate cancer.
Topics: Aged; Algorithms; Biopsy; Humans; Male; Middle Aged; Neoplasm Grading; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms
PubMed: 29259293
DOI: 10.1038/s41391-017-0024-7 -
The Journal of Urology Feb 2017Rabbit antiserum raised against the crude extract of normal human prostatic tissue contained antibodies to a prostatic tissue-specific antigen as shown by...
Rabbit antiserum raised against the crude extract of normal human prostatic tissue contained antibodies to a prostatic tissue-specific antigen as shown by immunoprecipitation techniques. Using this antiserum a prostate antigen was detected in normal, benign hypertrophic, and malignant prostatic tissues, but not in other human tissues. The prostate antigen was purified to homogeneity from prostatic tissues and showed a single protein band on analytical polyacrylamide gel electrophoresis and isoelectric focusing. This report thus presents the first demonstration of the purification of a prostate-specific antigen that does not represent prostatic acid phosphatase.
Topics: Animals; Electrophoresis, Polyacrylamide Gel; Female; Humans; Immune Sera; Immunoprecipitation; Isoelectric Focusing; Kallikreins; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Rabbits
PubMed: 28012750
DOI: 10.1016/j.juro.2016.10.100 -
Methods in Molecular Biology (Clifton,... 2019The Capillary Electrophoresis (CE) profile of isoforms (peaks) of a glycoprotein can be useful to show alterations in its posttranslational modifications (PTMs) linked...
The Capillary Electrophoresis (CE) profile of isoforms (peaks) of a glycoprotein can be useful to show alterations in its posttranslational modifications (PTMs) linked to diseases. These changes can modify the electrophoretic mobility of these isoforms in a minor extent and, therefore, very reproducible CE methods are needed to detect them. In this chapter, a method for the analysis of prostate-specific antigen (PSA) by Capillary Zone Electrophoresis (CZE) with UV detection is detailed. High reproducibility in the separation of a large number of PSA isoforms is achieved by performing capillary conditioning in acid media and by using a background electrolyte (BGE) at pH 8.0 formulated with decamethonium bromide and urea.
Topics: Electrophoresis, Capillary; Humans; Male; Prostate-Specific Antigen; Protein Isoforms; Time Factors
PubMed: 30847795
DOI: 10.1007/978-1-4939-9213-3_16 -
European Urology Oncology Jun 2021
Topics: Humans; Male; Prostate; Prostate-Specific Antigen; Prostatectomy; Salvage Therapy
PubMed: 33771485
DOI: 10.1016/j.euo.2021.03.003 -
Urologic Oncology Jul 2017Black men are more prone to harbor prostate cancer. They are more likely to succumb to this tumor than their White counterparts and may benefit from early detection and...
OBJECTIVE
Black men are more prone to harbor prostate cancer. They are more likely to succumb to this tumor than their White counterparts and may benefit from early detection and treatment. In this study, we assess the nationwide and regional disparity in prostate-specific antigen (PSA) screening for prostate cancer between Black men and non-Hispanic Whites (NHWs).
METHODS
A total of 247,079 (weighted 55,185,102) men, aged 40 to 99 years, who responded to the 2012 and 2014 behavioral risk factor surveillance system surveys were used for our analysis. End points consisted of self-reported PSA screening and self-reported nonrecommended PSA screening within 12 months of the interview. The latter was defined as screening in men with <10-year life expectancy. Available sociodemographic variables were used to predict these end points. The independent predictors from multivariate models were used to calculate the adjusted prevalence of PSA screening and nonrecommended PSA screening on a nationwide and regional level. These numbers were calculated for Blacks and NHWs separately and were compared between the 2 groups.
RESULTS
Prevalence of PSA screening was 30.7% in NHWs vs. 28.1% in Blacks (P<0.001). On a region-based analysis, New England, Middle Atlantic, South Atlantic, East North Central, East South Central, West South Central, and Mountain showed a significantly higher rate of PSA screening in NHWs as compared to Blacks (all P<0.001). Middle Atlantic had a significantly higher prevalence of nonrecommended screening in NHWs as compared to Blacks, whereas South Atlantic, West South Central, and Pacific had a significantly higher prevalence of nonrecommended screening in Blacks as compared to NHWs (all P<0.001). Overall, 43 states performed screening more frequently to NHWs, whereas only 8 states performed it more frequently to Black men. The nonrecommended screening was performed more frequently to NHWs in 19 states, whereas 24 states performed it more frequently to Black men.
CONCLUSION
Our study demonstrates that on a regional-level (and state-level), there are significant racial differences in overall and nonrecommended PSA screening across the United States. Further research is necessary to identify the reasons for the differences and help overcoming it.
Topics: Aged; Early Detection of Cancer; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Racial Groups
PubMed: 28256311
DOI: 10.1016/j.urolonc.2017.01.023 -
Urology Nov 2014
Topics: Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms
PubMed: 25443924
DOI: 10.1016/j.urology.2014.04.057 -
Current Opinion in Urology May 2017This article intends to review biomarkers derived from blood, urine, and tissue that can aid in the diagnosis of prostate cancer (PCa). (Review)
Review
PURPOSE OF REVIEW
This article intends to review biomarkers derived from blood, urine, and tissue that can aid in the diagnosis of prostate cancer (PCa).
RECENT FINDINGS
PCa screening requires tools that complement prostate-specific antigen (PSA) with a higher specificity for clinically significant disease. Novel blood biomarkers, such as the Prostate Health Index (phi) and 4Kscore, utilize isoforms of PSA to more accurately predict high-grade PCa than traditional tools such as PSA and the percentage free-to-total PSA. Several gene products associated with PCa can be detected in the urine through commercially available assays. PCa antigen 3 (PCA3), though approved for repeat biopsy decisions, appears inferior to other biomarkers such as phi for identifying aggressive disease. However, combinations of PCA3 with other urine assays have shown promising results. One tissue-based hypermethylation test, named ConfirmMDx, can also be used to determine the need for repeat biopsy in men with a prior negative biopsy.
SUMMARY
Several biomarkers have been developed to aid in the screening and diagnosis of PCa. Such tests are often indicated in men with moderately elevated PSA or history of a prior negative biopsy. Their use facilitates reduction of unnecessary biopsies without sacrificing the early diagnosis of clinically significant PCa.
Topics: Antigens, Neoplasm; Biomarkers, Tumor; Biopsy, Needle; Humans; Male; Predictive Value of Tests; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms
PubMed: 28212119
DOI: 10.1097/MOU.0000000000000384 -
The International Journal of Biological... Aug 2018Total PSA (tPSA) and free PSA (fPSA) are the most commonly used biomarkers for early detection of prostate cancer. Despite standardization efforts, many available PSA...
INTRODUCTION
Total PSA (tPSA) and free PSA (fPSA) are the most commonly used biomarkers for early detection of prostate cancer. Despite standardization efforts, many available PSA assays may still produce discordant results. In the present study, we compared four PSA assays calibrated to the WHO standards 96/670 and 96/668 for tPSA and fPSA, respectively.
METHODS
Within the scope of the Prostate Cancer Early Detection Study Based on a ''Baseline'' PSA Value in Young Men (PROBASE), we tested tPSA and fPSA in serum samples from 50 patients in the four different PROBASE sites using four WHO-calibrated assays from Roche (Elecsys, Cobas), Beckman-Coulter (Access-II) and Siemens (ADVIA Centaur). The comparison was performed using the Passing-Bablok regression method.
RESULTS
Compared to Access, the median tPSA levels for Centaur, Elecsys, and Cobas were +3%, +11%-20%, and +17%-23%, respectively, while for median fPSA levels the differences for Centaur, Elecsys, and Cobas were +49%, +29%-31%, and +22%, respectively.
DISCUSSION
Despite all investigated assays being WHO-calibrated, the Elecsys and Cobas tPSA assays produced considerably higher results than the Access and Centaur assays. Differences in fPSA-recovery between all investigated assays were even more pronounced. When applying the tPSA cutoff of 3.1 μg/L recommended for WHO-calibrated assays, the use of higher calibrated assays may lead to unnecessary prostate biopsies. Conversely, if the historical threshold of 4 μg/L is applied when using WHO-calibrated assays, it could lead to falsely omitted prostate biopsies.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Biopsy; Early Detection of Cancer; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Reference Standards; World Health Organization
PubMed: 29734838
DOI: 10.1177/1724600818754750