title: Association of metastin/a G-protein-coupled receptor signaling and Down syndrome critical region 1 in epithelial ovarian cancer.
abstract: It has been revealed that metastin/a G-protein-coupled receptor (AXOR12) signaling enhances the expression of Down syndrome critical region 1 (DSCR1), known to be duplicated in Down syndrome, and suppresses tumor metastasis in in vitro study. The aim of this study was to evaluate whether gene expression of metastin/AXOR12 signaling system is correlated with that of DSCR1 and consequently affect prognosis of patients with epithelial ovarian cancer.
  
  
  METHODS
  The expression levels of metastin, AXOR12, DSCR1 isoform 1 (DSCR1-1), DSCR1 isoform 4 (DSCR1-4), calcineurin, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene expression were analyzed by real-time quantitative reverse transcription-polymerase chain reaction in 102 epithelial ovarian cancer surgical specimens.
  
  
  RESULTS
  Patients were dichotomized into two groups having low and high expressions by using the median value as the cut-off A good agreement was noticed between metastin and AXOR12 gene expression levels (kappa coefficient; 0.73), however, the gene expression of metastin/AXOR12 signaling system was not significantly correlated with that of DSCR1-4. By univariate Cox regression analysis, the prognosis of the patients with low metastin and low AXOR12 gene expression was significantly worse than that of those with high metastin and high AXOR12 gene expression, respectively (p = 0.04 and 0.018). Combination of metastin and AXOR12 gene expression also had significant impact on patient prognosis (p = 0.045). The DSCR1-1, DSCR1-4 and calcineurin gene expressions did not significantly affect the prognosis.
  
  
  CONCLUSIONS
  The precise mechanism of metastin/ AXOR12 signaling for suppression of the invasive phenotype in vivo, especially in epithelial ovarian cancer, is still uncertain. Genes such as DSCR1 that are duplicated in Down syndrome might not play an important role in tumorigenesis of epithelial ovarian cancer.
authors.affiliation: Department of Tumor Biology, Kagawa Prefectural University of Health Sciences, Takamastu 761-0123, Japan. hata@chs.pref.kagawa.jp
authors.forename: Kohkichi
authors.initials: K
authors.lastname: Hata
authors.forename: Yoh
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Hidekatsu
authors.initials: H
authors.lastname: Nakai
authors.forename: Takashi
authors.initials: T
authors.lastname: Minami
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ohsaki
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Hirakawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hoshiai