Identification and validation of leucine-rich α-2-glycoprotein 1 as a noninvasive biomarker for improved precision in prostate cancer risk stratification

<p><strong>Background:</strong><br /> More accurate risk assessments are needed to improve prostate cancer management.</p><br /> <p><strong>Objective:</strong><br /> To identify blood-based protein biomarkers that provided prognostic infor...

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Main Authors: Guldvik, IJ, Zuber, V, Braadland, PR, Grytli, HH, Ramberg, H, Lilleby, W, Thiede, B, Zucknick, M, Saatcioglu, F, Gislefoss, R, Kvåle, R, George, A, Grönberg, H, Wiklund, F, Neal, DE, Gnanapragasam, VJ, Taskén, KA, Mills, IG
Format: Journal article
Language:English
Published: Elsevier 2020
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author Guldvik, IJ
Zuber, V
Braadland, PR
Grytli, HH
Ramberg, H
Lilleby, W
Thiede, B
Zucknick, M
Saatcioglu, F
Gislefoss, R
Kvåle, R
George, A
Grönberg, H
Wiklund, F
Neal, DE
Gnanapragasam, VJ
Taskén, KA
Mills, IG
author_facet Guldvik, IJ
Zuber, V
Braadland, PR
Grytli, HH
Ramberg, H
Lilleby, W
Thiede, B
Zucknick, M
Saatcioglu, F
Gislefoss, R
Kvåle, R
George, A
Grönberg, H
Wiklund, F
Neal, DE
Gnanapragasam, VJ
Taskén, KA
Mills, IG
author_sort Guldvik, IJ
collection OXFORD
description <p><strong>Background:</strong><br /> More accurate risk assessments are needed to improve prostate cancer management.</p><br /> <p><strong>Objective:</strong><br /> To identify blood-based protein biomarkers that provided prognostic information for risk stratification.</p><br /> <p><strong>Design, Setting, and Participants:</strong><br /> Mass spectrometry was used to identify biomarker candidates from blood, and validation studies were performed in four independent cohorts retrospectively collected between 1988 and 2015.</p><br /> <p><strong>Outcome Measurements and Statistical Analysis:</strong><br /> The primary outcome objectives were progression-free survival, prostate cancer–specific survival (PCSS), and overall survival. Statistical analyses to assess survival and model performance were performed.</p><br /> <p><strong>Results and Limitation:</strong><br /> Serum leucine-rich α-2-glycoprotein 1 (LRG1) was found to be elevated in fatal prostate cancer. LRG1 provided prognostic information independent of metastasis and increased the accuracy in predicting PCSS, particularly in the first 3 yr. A high LRG1 level is associated with an average of two-fold higher risk of disease-progression and mortality in both high-risk and metastatic patients. However, our study design, with a retrospective analysis of samples spanning several decades back, limits the assessment of the clinical utility of LRG1 in today’s clinical practice. Thus, independent prospective studies are needed to establish LRG1 as a clinically useful biomarker for patient management.</p><br /> <p><strong>Conclusions:</strong><br /> High blood levels of LRG1 are unfavourable in newly diagnosed high-risk and metastatic prostate cancer, and LRG1 increased the accuracy of risk stratification of prostate cancer patients.</p><br /> <p><strong>Patient Summary:</strong><br /> High blood levels of leucine-rich α-2-glycoprotein 1 are unfavourable in newly diagnosed high-risk and metastatic prostate cancer.</p>
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spelling oxford-uuid:e8e889a7-3ba0-4a65-ba17-e02f617c86842022-03-27T10:50:21ZIdentification and validation of leucine-rich α-2-glycoprotein 1 as a noninvasive biomarker for improved precision in prostate cancer risk stratificationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e8e889a7-3ba0-4a65-ba17-e02f617c8684EnglishSymplectic ElementsElsevier2020Guldvik, IJZuber, VBraadland, PRGrytli, HHRamberg, HLilleby, WThiede, BZucknick, MSaatcioglu, FGislefoss, RKvåle, RGeorge, AGrönberg, HWiklund, FNeal, DEGnanapragasam, VJTaskén, KAMills, IG<p><strong>Background:</strong><br /> More accurate risk assessments are needed to improve prostate cancer management.</p><br /> <p><strong>Objective:</strong><br /> To identify blood-based protein biomarkers that provided prognostic information for risk stratification.</p><br /> <p><strong>Design, Setting, and Participants:</strong><br /> Mass spectrometry was used to identify biomarker candidates from blood, and validation studies were performed in four independent cohorts retrospectively collected between 1988 and 2015.</p><br /> <p><strong>Outcome Measurements and Statistical Analysis:</strong><br /> The primary outcome objectives were progression-free survival, prostate cancer–specific survival (PCSS), and overall survival. Statistical analyses to assess survival and model performance were performed.</p><br /> <p><strong>Results and Limitation:</strong><br /> Serum leucine-rich α-2-glycoprotein 1 (LRG1) was found to be elevated in fatal prostate cancer. LRG1 provided prognostic information independent of metastasis and increased the accuracy in predicting PCSS, particularly in the first 3 yr. A high LRG1 level is associated with an average of two-fold higher risk of disease-progression and mortality in both high-risk and metastatic patients. However, our study design, with a retrospective analysis of samples spanning several decades back, limits the assessment of the clinical utility of LRG1 in today’s clinical practice. Thus, independent prospective studies are needed to establish LRG1 as a clinically useful biomarker for patient management.</p><br /> <p><strong>Conclusions:</strong><br /> High blood levels of LRG1 are unfavourable in newly diagnosed high-risk and metastatic prostate cancer, and LRG1 increased the accuracy of risk stratification of prostate cancer patients.</p><br /> <p><strong>Patient Summary:</strong><br /> High blood levels of leucine-rich α-2-glycoprotein 1 are unfavourable in newly diagnosed high-risk and metastatic prostate cancer.</p>
spellingShingle Guldvik, IJ
Zuber, V
Braadland, PR
Grytli, HH
Ramberg, H
Lilleby, W
Thiede, B
Zucknick, M
Saatcioglu, F
Gislefoss, R
Kvåle, R
George, A
Grönberg, H
Wiklund, F
Neal, DE
Gnanapragasam, VJ
Taskén, KA
Mills, IG
Identification and validation of leucine-rich α-2-glycoprotein 1 as a noninvasive biomarker for improved precision in prostate cancer risk stratification
title Identification and validation of leucine-rich α-2-glycoprotein 1 as a noninvasive biomarker for improved precision in prostate cancer risk stratification
title_full Identification and validation of leucine-rich α-2-glycoprotein 1 as a noninvasive biomarker for improved precision in prostate cancer risk stratification
title_fullStr Identification and validation of leucine-rich α-2-glycoprotein 1 as a noninvasive biomarker for improved precision in prostate cancer risk stratification
title_full_unstemmed Identification and validation of leucine-rich α-2-glycoprotein 1 as a noninvasive biomarker for improved precision in prostate cancer risk stratification
title_short Identification and validation of leucine-rich α-2-glycoprotein 1 as a noninvasive biomarker for improved precision in prostate cancer risk stratification
title_sort identification and validation of leucine rich α 2 glycoprotein 1 as a noninvasive biomarker for improved precision in prostate cancer risk stratification
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