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.
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Handling editor Dhirendra Govender.
Contributors GK, KDB, JDB, KB and MAR designed the study. GK drafted the manuscript which was critically reviewed by all other authors. BGT, JDB, KB and MAR provided study supervision. KDB and MAR contributed to data collection. GK, HVS and RN performed data analysis and all authors contributed to data interpretation.
Funding This study is sponsored by grants from the Danish Cancer Society and Beckett-Foundation.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval The study was approved by the Danish National Committee on Health Research Ethics (journal no. H-6-2014-111) and the Danish Data Protection Agency (file no. 2006-1-6256)
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available on reasonable request.