Identification and Validation of Leucine-rich α-2-glycoprotein 1 as a Noninvasive Biomarker for Improved Precision in Prostate Cancer Risk Stratification

More accurate risk assessments are needed to improve prostate cancer management. To identify blood-based protein biomarkers that provided prognostic information for risk stratification. 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. 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. 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. 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. High blood levels of leucine-rich α-2-glycoprotein 1 are unfavourable in newly diagnosed high-risk and metastatic prostate cancer. High blood levels of leucine-rich α-2-glycoprotein 1 (LRG1) is unfavourable in patients with newly diagnosed high-risk or metastatic prostate cancer. Implementation of a blood test for LRG1 alongside standard risk stratification schemes could provide higher precision in treatment decisions.