The Percentage of Free PSA and Urinary Markers Distinguish Prostate Cancer from Benign Hyperplasia and Contribute to a More Accurate Indication for Prostate Biopsy
The main advantage of urinary biomarkers is their noninvasive character and the ability to detect multifocal prostate cancer (CaP). We have previously implemented a quadruplex assay of urinary markers into clinical practice (<i>PCA3, AMACR, TRPM8</i> and <i>MSMB</i> with <...
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MDPI AG
2020-06-01
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author | Zlata Huskova Jana Knillova Zdenek Kolar Jana Vrbkova Milan Kral Jan Bouchal |
author_facet | Zlata Huskova Jana Knillova Zdenek Kolar Jana Vrbkova Milan Kral Jan Bouchal |
author_sort | Zlata Huskova |
collection | DOAJ |
description | The main advantage of urinary biomarkers is their noninvasive character and the ability to detect multifocal prostate cancer (CaP). We have previously implemented a quadruplex assay of urinary markers into clinical practice (<i>PCA3, AMACR, TRPM8</i> and <i>MSMB</i> with <i>KLK3</i> normalization). In this study, we aimed to validate it in a larger cohort with serum PSA 2.5–10 ng/mL and test other selected transcripts and clinical parameters, including the percentage of free prostate-specific antigen (PSA) (% free PSA) and inflammation. In the main cohort of 299 men, we tested the quadruplex transcripts. In a subset of 146 men, we analyzed additional transcripts (<i>CD45, EPCAM, EZH2, Ki67, PA2G4, PSGR, RHOA</i> and <i>TBP</i>). After a prostate massage, the urine was collected, RNA isolated from a cell sediment and qRT-PCR performed. Ct values of <i>KLK3</i> (i.e., PSA) were strongly correlated with Ct values of other genes which play a role in CaP (i.e., <i>PCA3, AMACR, TRPM8, MSMB</i> and <i>PSGR</i>). <i>AMACR, PCA3, TRPM8</i> and <i>EZH2</i> mRNA expression, as well as % free PSA, were significantly different for BPH and CaP. The best combined model (% free PSA plus <i>PCA3</i> and <i>AMACR</i>) achieved an AUC of 0.728 in the main cohort. In the subset of patients, the best AUC 0.753 was achieved for the combination of <i>PCA3</i>, % free PSA, <i>EPCAM</i> and <i>PSGR</i>. <i>PCA3</i> mRNA was increased in patients with inflammation, however, this did not affect the stratification of patients indicated for prostate biopsy. In conclusion, the percentage of free PSA and urinary markers contribute to a more accurate indication for prostate biopsy. |
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spelling | doaj.art-ea4dd2ea70d447e4aed0abb1b00d4a622023-11-20T04:56:36ZengMDPI AGBiomedicines2227-90592020-06-018617310.3390/biomedicines8060173The Percentage of Free PSA and Urinary Markers Distinguish Prostate Cancer from Benign Hyperplasia and Contribute to a More Accurate Indication for Prostate BiopsyZlata Huskova0Jana Knillova1Zdenek Kolar2Jana Vrbkova3Milan Kral4Jan Bouchal5Department of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University and University Hospital, 779 00 Olomouc, Czech RepublicDepartment of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University and University Hospital, 779 00 Olomouc, Czech RepublicDepartment of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University and University Hospital, 779 00 Olomouc, Czech RepublicInstitute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, 779 00 Olomouc, Czech RepublicDepartment of Urology, University Hospital, 779 00 Olomouc, Czech RepublicDepartment of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University and University Hospital, 779 00 Olomouc, Czech RepublicThe main advantage of urinary biomarkers is their noninvasive character and the ability to detect multifocal prostate cancer (CaP). We have previously implemented a quadruplex assay of urinary markers into clinical practice (<i>PCA3, AMACR, TRPM8</i> and <i>MSMB</i> with <i>KLK3</i> normalization). In this study, we aimed to validate it in a larger cohort with serum PSA 2.5–10 ng/mL and test other selected transcripts and clinical parameters, including the percentage of free prostate-specific antigen (PSA) (% free PSA) and inflammation. In the main cohort of 299 men, we tested the quadruplex transcripts. In a subset of 146 men, we analyzed additional transcripts (<i>CD45, EPCAM, EZH2, Ki67, PA2G4, PSGR, RHOA</i> and <i>TBP</i>). After a prostate massage, the urine was collected, RNA isolated from a cell sediment and qRT-PCR performed. Ct values of <i>KLK3</i> (i.e., PSA) were strongly correlated with Ct values of other genes which play a role in CaP (i.e., <i>PCA3, AMACR, TRPM8, MSMB</i> and <i>PSGR</i>). <i>AMACR, PCA3, TRPM8</i> and <i>EZH2</i> mRNA expression, as well as % free PSA, were significantly different for BPH and CaP. The best combined model (% free PSA plus <i>PCA3</i> and <i>AMACR</i>) achieved an AUC of 0.728 in the main cohort. In the subset of patients, the best AUC 0.753 was achieved for the combination of <i>PCA3</i>, % free PSA, <i>EPCAM</i> and <i>PSGR</i>. <i>PCA3</i> mRNA was increased in patients with inflammation, however, this did not affect the stratification of patients indicated for prostate biopsy. In conclusion, the percentage of free PSA and urinary markers contribute to a more accurate indication for prostate biopsy.https://www.mdpi.com/2227-9059/8/6/173prostate cancer% free PSA<i>PCA3</i><i>AMACR</i>inflammation |
spellingShingle | Zlata Huskova Jana Knillova Zdenek Kolar Jana Vrbkova Milan Kral Jan Bouchal The Percentage of Free PSA and Urinary Markers Distinguish Prostate Cancer from Benign Hyperplasia and Contribute to a More Accurate Indication for Prostate Biopsy Biomedicines prostate cancer % free PSA <i>PCA3</i> <i>AMACR</i> inflammation |
title | The Percentage of Free PSA and Urinary Markers Distinguish Prostate Cancer from Benign Hyperplasia and Contribute to a More Accurate Indication for Prostate Biopsy |
title_full | The Percentage of Free PSA and Urinary Markers Distinguish Prostate Cancer from Benign Hyperplasia and Contribute to a More Accurate Indication for Prostate Biopsy |
title_fullStr | The Percentage of Free PSA and Urinary Markers Distinguish Prostate Cancer from Benign Hyperplasia and Contribute to a More Accurate Indication for Prostate Biopsy |
title_full_unstemmed | The Percentage of Free PSA and Urinary Markers Distinguish Prostate Cancer from Benign Hyperplasia and Contribute to a More Accurate Indication for Prostate Biopsy |
title_short | The Percentage of Free PSA and Urinary Markers Distinguish Prostate Cancer from Benign Hyperplasia and Contribute to a More Accurate Indication for Prostate Biopsy |
title_sort | percentage of free psa and urinary markers distinguish prostate cancer from benign hyperplasia and contribute to a more accurate indication for prostate biopsy |
topic | prostate cancer % free PSA <i>PCA3</i> <i>AMACR</i> inflammation |
url | https://www.mdpi.com/2227-9059/8/6/173 |
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