metastin和一种G蛋白偶联受体（AXOR12）在上皮性卵巢癌中的表达

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

作者信息

Hata Kohkichi, Dhar Dipok Kumar, Watanabe Yoh, Nakai Hidekatsu, Hoshiai Hiroshi

机构信息

Department of Tumor Biology, Kagawa Prefectural University of Health Sciences, Takamastu 761-0123, Japan.

出版信息

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

DOI:10.1016/j.ejca.2007.03.004

PMID:17442564

Abstract

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.

摘要

背景

Metastin是KiSS-1基因的产物，是一种G蛋白偶联受体（AXOR12）的配体，是一种强大的转移抑制因子。本研究的目的是评估Metastin和AXOR12基因表达是否影响上皮性卵巢癌患者的预后。

方法

采用实时定量逆转录-聚合酶链反应分析76例上皮性卵巢癌手术标本中Metastin、AXOR12和甘油醛-3-磷酸脱氢酶（GAPDH）基因的表达水平。它们的表达（Metastin/GAPDH和AXOR12/GAPDH比值）与临床结果相关。此外，通过组织切片原位杂交检测Metastin和AXOR12 mRNA的细胞分布。

结果

Metastin和AXOR12的mRNA表达中位数及范围分别为0.047和0.01 - 13.57，以及4.00和0.011 - 135.13。以中位数为界值将患者分为低表达和高表达两组。发现Metastin和AXOR12基因表达水平之间有良好的一致性（kappa系数；0.74）。切除后残留肿瘤的存在与Metastin（P = 0.0084）和AXOR12（P = 0.0148）基因表达呈负相关，表明这些基因的低表达与更具侵袭性的晚期肿瘤有关。单因素Cox回归分析显示，AXOR12基因低表达患者的预后明显差于AXOR12基因高表达患者（P = 0.030）。Metastin和AXOR12基因表达水平的联合也与预后显著相关（P = 0.049）。在卵巢上皮癌细胞中检测到Metastin和AXOR12的转录本。