Expression of metastin and a G-protein-coupled receptor (AXOR12) in epithelial ovarian cancer

Eur J Cancer. 2007 Jun;43(9):1452-9. doi: 10.1016/j.ejca.2007.03.004. Epub 2007 Apr 17.


Background: Metastin, a product of the KiSS-1 gene, is a ligand for a G-protein-coupled receptor (AXOR12) and is a strong suppressant of metastasis. The aim of this study was to evaluate whether metastin and AXOR12 gene expressions affect prognosis of patients with epithelial ovarian cancer.

Methods: The expression levels of metastin, AXOR12 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene expression were analysed by the real-time quantitative reverse transcription-polymerase chain reaction in 76 epithelial ovarian cancer surgical specimens. Their expression (metastin/GAPDH and AXOR12/GAPDH ratios) was correlated with the clinical findings. Furthermore, cellular distribution of metastin and AXOR12 mRNA was examined by in situ hybridisation on tissue sections.

Results: The median and range of mRNA expression for metastin and AXOR12 were 0.047 and 0.01-13.57, and 4.00 and 0.011-135.13, respectively. Patients were dichotomised into two groups having low and high expressions by using the median value as the cutoff. A good agreement was noticed between metastin and AXOR12 gene expression levels (kappa coefficient; 0.74). The presence of residual tumour following resection was negatively associated with metastin (P=0.0084) and AXOR12 (P=0.0148) gene expressions indicating an association of low expression of these genes in more aggressive, and advanced tumours. By univariate Cox regression analysis, the prognosis of the patients with low AXOR12 gene expression was significantly worse than those with high AXOR12 gene expression (P=0.030). The combination of metastin and AXOR12 gene expression level was also significantly associated with the prognosis (P=0.049). Transcripts for both metastin and AXOR12 were detected in the epithelial ovarian carcinoma cells.

Conclusions: These results present a new insight into the understanding of the biological behaviour of epithelial ovarian cancer. Metastin/AXOR12 signalling may suppress the invasive phenotype of epithelial ovarian cancer.

MeSH terms

  • Adult
  • Aged
  • Female
  • Gene Expression
  • Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+) / genetics
  • Humans
  • Kisspeptins
  • Middle Aged
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / mortality
  • Prognosis
  • RNA, Messenger / metabolism
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, Kisspeptin-1
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Analysis
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*


  • KISS1 protein, human
  • KISS1R protein, human
  • Kisspeptins
  • Neoplasm Proteins
  • RNA, Messenger
  • Receptors, G-Protein-Coupled
  • Receptors, Kisspeptin-1
  • Tumor Suppressor Proteins
  • Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+)