BACKGROUND: Novel biomarkers for prostate cancer (PC) are urgently needed.
This study investigates the expression, epigenetic regulation, and prognostic potential of ANPEP in PC.
METHODS: Aminopeptidase N (APN; encoded by ANPEP) expression was analysed by immunohistochemistry using tissue microarrays representing 267 radical prostatectomy (RP) and 111 conservatively treated (CT) PC patients. Clinical end points were recurrence-free survival (RFS) and cancer-specific survival (CSS), respectively. The ANPEP promoter methylation levels were determined by bisulphite sequencing or MethyLight analysis in 278 nonmalignant and PC tissue samples, and in cell lines.
RESULTS: The APN expression was significantly downregulated in PC compared with nonmalignant prostate tissue samples. Aberrant promoter hypermethylation was frequently observed in PC tissue samples, and 5-aza-2'-deoxycytidine induced ANPEP expression in three hypermethylated prostate cell lines, suggesting epigenetic silencing. Negative APN immunoreactivity was significantly associated with short RFS and short CSS in the RP and CT cohort, respectively, independently of routine clinicopathological predictors. Combining APN with a known angiogenesis marker (vascular endothelial growth factor or microvessel density) improved risk prediction significantly in both cohorts.
CONCLUSION: Our results suggest negative APN immunoreactivity as a new independent adverse prognostic factor for patients with clinically localised PC and, furthermore, that epigenetic mechanisms are involved in silencing of ANPEP in PC.
Written by:
Sørensen KD, Abildgaard MO, Haldrup C, Ulhøi BP, Kristensen H, Strand S, Parker C, Høyer S, Borre M, Ørntoft TF. Are you the author?
Department of Molecular Medicine, Aarhus University Hospital, Brendstrupgaardsvej 100, DK-8200 Aarhus N, Aarhus, Denmark
Reference: Br J Cancer. 2013 Feb 5;108(2):420-8
doi: 10.1038/bjc.2012.549
PubMed Abstract
PMID: 23322201
