Identification and validation of leucine-rich alpha-2-glycoprotein 1 as a noninvasive biomarker for improved precision in prostate cancer risk stratification
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background
More accurate risk assessments are needed to improve prostate cancer management.
Objective
To identify blood-based protein biomarkers that provided prognostic information for risk stratification.
Design, setting, and participants
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.
Outcome measurements and statistical analysis
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.
Results and limitation
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.
Conclusions
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.
Patient summary
High blood levels of leucine-rich α-2-glycoprotein 1 are unfavourable in newly diagnosed high-risk and metastatic prostate cancer.
More accurate risk assessments are needed to improve prostate cancer management.
Objective
To identify blood-based protein biomarkers that provided prognostic information for risk stratification.
Design, setting, and participants
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.
Outcome measurements and statistical analysis
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.
Results and limitation
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.
Conclusions
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.
Patient summary
High blood levels of leucine-rich α-2-glycoprotein 1 are unfavourable in newly diagnosed high-risk and metastatic prostate cancer.
Date Issued
2020-10-21
Date Acceptance
2020-08-21
Citation
EUROPEAN UROLOGY OPEN SCIENCE, 2020, 21, pp.51-60
ISSN
2666-1691
Publisher
ELSEVIER
Start Page
51
End Page
60
Journal / Book Title
EUROPEAN UROLOGY OPEN SCIENCE
Volume
21
Copyright Statement
© 2020 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article
under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000583275500012&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Urology & Nephrology
Biomarker
Leucine-rich alpha-2-glycoprotein 1
Noninvasive
Prostate cancer
LRG1 PROMOTES ANGIOGENESIS
DISEASE-ACTIVITY BIOMARKER
ALPHA-2 GLYCOPROTEIN
COLORECTAL-CANCER
PROGNOSTIC-FACTOR
SERUM BIOMARKER
EXPRESSION
MIGRATION
DIAGNOSIS
ANTIGEN
Publication Status
Published
Date Publish Online
2020-10-13