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Predictive value of AZGP1 following radical prostatectomy for prostate cancer: a cohort study and meta-analysis

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AIMS: Zinc-alpha 2-glycoprotein (AZGP1) is a promising tissue biomarker to predict outcomes in men undergoing treatment for localised prostate cancer (PCa). We aimed to examine the association between AZGP1 expression and the endpoints: risk of biochemical failure (BF), initiating castration-based treatment, developing castration-resistant PCa (CRPC) and PCa-specific mortality following radical prostatectomy (RP).

METHODS: The study included a prospective cohort of 302 patients who underwent RP for PCa from 2002 to 2005. AZGP1 expression was analysed using immunohistochemistry on tissue microarray RP specimens and was scored semiquantitively as low or high expression. Risk of all endpoints was analysed using stratified cumulative incidences and cause-specific Cox regression, and validated with receiver operating curves, calibration and discrimination in competing-risk analyses. A meta-analysis was performed including previous studies investigating AZGP1 expression and risk of BF following RP.

RESULTS: Median time of follow-up was 14.0 years. The cumulative incidence of all endpoints was significantly higher in patients with low AZGP1 expression compared with patients with high AZGP1 expression (p<0.001). In a multivariate analysis, low AZGP1 expression increases the risk of BF (HR 2.7; 95% CI 1.9 to 3.8; p<0.0001), castration-based treatment (HR 2.2; 95% CI 1.2 to 4.2; p=0.01) and CRPC (HR 2.3; 95% CI 1.1 to 5.0; p=0.03). Validation showed a low risk of prediction error and a high model performance for all endpoints. In a meta-analysis, low AZGP1 was associated with BF (HR 1.7; 95% CI 1.2 to 2.5).

CONCLUSIONS: Low AZGP1 expression is associated with the risk of aggressive time-dependent outcomes in men undergoing RP for localised PCa.

Original languageEnglish
JournalJournal of Clinical Pathology
Volume72
Issue number10
Pages (from-to)696-704
Number of pages9
ISSN0021-9746
DOIs
Publication statusPublished - 1 Oct 2019

    Research areas

  • Biomarkers, Tumor/metabolism, Carrier Proteins/metabolism, Cohort Studies, Glycoproteins/metabolism, Humans, Immunohistochemistry, Male, Multivariate Analysis, Prospective Studies, Prostate/metabolism, Prostatectomy, Prostatic Neoplasms/metabolism, Tissue Array Analysis, cancer, prostate, immunohistochemistry

ID: 58147667