title: The role of HOXC6 in prostate cancer development.
abstract: 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.
authors: Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.|Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.|Department of Urology, Cipto Mangunkusumo Hospital, Department Surgery, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia.
authors: Agus Rizal A H
authors: AR
authors: Hamid
authors: Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors: A Marije
authors: AM
authors: Hoogland
authors: NovioGendix BV, Nijmegen, The Netherlands.
authors: Frank
authors: F
authors: Smit
authors: NovioGendix BV, Nijmegen, The Netherlands.
authors: Sander
authors: S
authors: Jannink
authors: Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.|Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors: Cindy
authors: C
authors: van Rijt-van de Westerlo
authors: Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.|Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors: Cornelius F J
authors: CF
authors: Jansen
authors: Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors: Geert J L H
authors: GJ
authors: van Leenders
authors: Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.|Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors: Gerald W
authors: GW
authors: Verhaegh
authors: Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.|Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors: Jack A
authors: JA
authors: Schalken
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D011379:Prognosis; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
chemical_list: C094289:HOXC6 protein, human; D018398:Homeodomain Proteins
keywords: androgens; homeobox gene; prostate cancer; urinary biomarker