BACKGROUND Homeobox (HOX) genes, which are involved in organ development and homeostasis, have been shown to be involved in normal prostate- and PCA development. In this study, we investigate the expression levels of the HOX A-D genes in PCA. The functional relevance and potential of HOX gene as biomarkers are explored. METHODS We evaluated HOX gene expression in prostate tissues of different grade and stage and related the outcome to clinical parameters. We analyzed AR regulation and function of HOXC6 in PCA cell lines. We developed a urine-based HOXC6 mRNA assay for diagnostic purposes. RESULTS HOXC6 was one of the most upregulated HOX genes in all primary, metastasized, and castration-resistant PCA. HOXC6 upregulation was specific to the epithelial component of PCA, and HOXC6 was shown to be involved in epithelial cell proliferation. HOXC6 expression was not influenced by androgens nor by treatments targeting the AR signaling pathway. HOXC6 expression was not related to a prognosis after radical prostatectomy, that is, biochemical or local recurrence. We successfully developed an assay for HOXC6 mRNA detection in urine and confirmed that HOXC6 levels are higher in PCA patients. CONCLUSIONS HOXC6 has a role in all PCA stages, particularly in PCA cell proliferation. Due to its stable expression, HOXC6 is a novel candidate biomarker for PCA not only in early detection but also for monitoring of progression or response to therapy. Prostate 75:1868-1876, 2015.

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The Prostate
Department of Pathology