The Urine Biomarker PUR-4 Is Positively Associated with the Amount of Gleason 4 in Human Prostate Cancers

The Prostate Urine Risk (PUR) biomarker is a four-group classifier for predicting outcome in patients prior to biopsy and for men on active surveillance. The four categories correspond to the probabilities of the presence of normal tissue (PUR-1), D’Amico low-risk (PUR-2), intermediate-risk (PUR-3),...

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Main Authors: Richard Y. Ball, Ryan Cardenas, Mark S. Winterbone, Marcelino Y. Hanna, Chris Parker, Rachel Hurst, Daniel S. Brewer, Lauren D’Sa, Rob Mills, Colin S. Cooper, Jeremy Clark
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:Life
Subjects:
Online Access:https://www.mdpi.com/2075-1729/11/11/1172
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author Richard Y. Ball
Ryan Cardenas
Mark S. Winterbone
Marcelino Y. Hanna
Chris Parker
Rachel Hurst
Daniel S. Brewer
Lauren D’Sa
Rob Mills
Colin S. Cooper
Jeremy Clark
author_facet Richard Y. Ball
Ryan Cardenas
Mark S. Winterbone
Marcelino Y. Hanna
Chris Parker
Rachel Hurst
Daniel S. Brewer
Lauren D’Sa
Rob Mills
Colin S. Cooper
Jeremy Clark
author_sort Richard Y. Ball
collection DOAJ
description The Prostate Urine Risk (PUR) biomarker is a four-group classifier for predicting outcome in patients prior to biopsy and for men on active surveillance. The four categories correspond to the probabilities of the presence of normal tissue (PUR-1), D’Amico low-risk (PUR-2), intermediate-risk (PUR-3), and high-risk (PUR-4) prostate cancer. In the current study we investigate how the PUR-4 status is linked to Gleason grade, prostate volume, and tumor volume as assessed from biopsy (<i>n</i> = 215) and prostatectomy (<i>n</i> = 9) samples. For biopsy data PUR-4 status alone was linked to Gleason Grade group (GG) (Spearman’s, <i>ρ</i> = 0.58, <i>p</i> < 0.001 trend). To assess the impact of tumor volume each GG was dichotomized into Small and Large volume cancers relative to median volume. For GG1 (Gleason Pattern 3 + 3) cancers volume had no impact on PUR-4 status. In contrast for GG2 (3 + 4) and GG3 (4 + 3) cancers PUR-4 levels increased in large volume cancers with statistical significance observed for GG2 (<i>p</i> = 0.005; Games-Howell). These data indicated that PUR-4 status is linked to the presence of Gleason Pattern 4. To test this observation tumor burden and Gleason Pattern were assessed in nine surgically removed and sectioned prostates allowing reconstruction of 3D maps. PUR-4 was not correlated with Gleason Pattern 3 amount, total tumor volume or prostate size. A strong correlation was observed between amount of Gleason Pattern 4 tumor and PUR-4 signature (<i>r</i> = 0.71, <i>p</i> = 0.034, Pearson’s). These observations shed light on the biological significance of the PUR biomarker and support its use as a non-invasive means of assessing the presence of clinically significant prostate cancer.
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spelling doaj.art-da05f8c2ac47466c831676bc9de0f3252023-11-23T00:03:54ZengMDPI AGLife2075-17292021-11-011111117210.3390/life11111172The Urine Biomarker PUR-4 Is Positively Associated with the Amount of Gleason 4 in Human Prostate CancersRichard Y. Ball0Ryan Cardenas1Mark S. Winterbone2Marcelino Y. Hanna3Chris Parker4Rachel Hurst5Daniel S. Brewer6Lauren D’Sa7Rob Mills8Colin S. Cooper9Jeremy Clark10Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich NR4 7UY, UKNorwich Medical School, University of East Anglia, Norwich NR4 7TJ, UKNorwich Medical School, University of East Anglia, Norwich NR4 7TJ, UKUrology Department Castle Hill, Hull University Teaching Hospital, Castle Rd, Cottingham HU16 5JQ, UKInstitute of Cancer Research, Sutton SM2 5NG, UKNorwich Medical School, University of East Anglia, Norwich NR4 7TJ, UKNorwich Medical School, University of East Anglia, Norwich NR4 7TJ, UKNorfolk and Norwich University Hospitals NHS Foundation Trust, Norwich NR4 7UY, UKNorfolk and Norwich University Hospitals NHS Foundation Trust, Norwich NR4 7UY, UKNorwich Medical School, University of East Anglia, Norwich NR4 7TJ, UKNorwich Medical School, University of East Anglia, Norwich NR4 7TJ, UKThe Prostate Urine Risk (PUR) biomarker is a four-group classifier for predicting outcome in patients prior to biopsy and for men on active surveillance. The four categories correspond to the probabilities of the presence of normal tissue (PUR-1), D’Amico low-risk (PUR-2), intermediate-risk (PUR-3), and high-risk (PUR-4) prostate cancer. In the current study we investigate how the PUR-4 status is linked to Gleason grade, prostate volume, and tumor volume as assessed from biopsy (<i>n</i> = 215) and prostatectomy (<i>n</i> = 9) samples. For biopsy data PUR-4 status alone was linked to Gleason Grade group (GG) (Spearman’s, <i>ρ</i> = 0.58, <i>p</i> < 0.001 trend). To assess the impact of tumor volume each GG was dichotomized into Small and Large volume cancers relative to median volume. For GG1 (Gleason Pattern 3 + 3) cancers volume had no impact on PUR-4 status. In contrast for GG2 (3 + 4) and GG3 (4 + 3) cancers PUR-4 levels increased in large volume cancers with statistical significance observed for GG2 (<i>p</i> = 0.005; Games-Howell). These data indicated that PUR-4 status is linked to the presence of Gleason Pattern 4. To test this observation tumor burden and Gleason Pattern were assessed in nine surgically removed and sectioned prostates allowing reconstruction of 3D maps. PUR-4 was not correlated with Gleason Pattern 3 amount, total tumor volume or prostate size. A strong correlation was observed between amount of Gleason Pattern 4 tumor and PUR-4 signature (<i>r</i> = 0.71, <i>p</i> = 0.034, Pearson’s). These observations shed light on the biological significance of the PUR biomarker and support its use as a non-invasive means of assessing the presence of clinically significant prostate cancer.https://www.mdpi.com/2075-1729/11/11/1172prostatecancerurinePURPUR-4Gleason pattern 4
spellingShingle Richard Y. Ball
Ryan Cardenas
Mark S. Winterbone
Marcelino Y. Hanna
Chris Parker
Rachel Hurst
Daniel S. Brewer
Lauren D’Sa
Rob Mills
Colin S. Cooper
Jeremy Clark
The Urine Biomarker PUR-4 Is Positively Associated with the Amount of Gleason 4 in Human Prostate Cancers
Life
prostate
cancer
urine
PUR
PUR-4
Gleason pattern 4
title The Urine Biomarker PUR-4 Is Positively Associated with the Amount of Gleason 4 in Human Prostate Cancers
title_full The Urine Biomarker PUR-4 Is Positively Associated with the Amount of Gleason 4 in Human Prostate Cancers
title_fullStr The Urine Biomarker PUR-4 Is Positively Associated with the Amount of Gleason 4 in Human Prostate Cancers
title_full_unstemmed The Urine Biomarker PUR-4 Is Positively Associated with the Amount of Gleason 4 in Human Prostate Cancers
title_short The Urine Biomarker PUR-4 Is Positively Associated with the Amount of Gleason 4 in Human Prostate Cancers
title_sort urine biomarker pur 4 is positively associated with the amount of gleason 4 in human prostate cancers
topic prostate
cancer
urine
PUR
PUR-4
Gleason pattern 4
url https://www.mdpi.com/2075-1729/11/11/1172
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