Association of metastin/a G-protein-coupled receptor signaling and Down syndrome critical region 1 in epithelial ovarian cancer.
Association of metastin/a G-protein-coupled receptor signaling and Down syndrome critical region 1 in epithelial ovarian cancer.
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发表时间：
2009-02
影响因子：
2
通讯作者：
K. Hata;Yoh Watanabe;H. Nakai;T. Minami;H. Ohsaki;E. Hirakawa;H. Hoshiai
中科院分区：
文献类型：
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作者：
K. Hata;Yoh Watanabe;H. Nakai;T. Minami;H. Ohsaki;E. Hirakawa;H. Hoshiai
在体外研究中，metastin/a G蛋白偶联受体（AXOR 12）信号传导增强了唐氏综合征关键区1（DSCR 1）的表达，并抑制了肿瘤转移，已知DSCR 1在唐氏综合征中复制。本研究旨在探讨卵巢上皮性癌组织中metastin/AXOR 12信号系统基因表达与DSCR 1基因表达的相关性及其对预后的影响。患者和方法采用实时定量逆转录聚合酶链反应分析102例上皮性卵巢癌手术标本中metastin、AXOR 12、DSCR 1亚型1（DSCR 1 -1）、DSCR 1亚型4（DSCR 1 -4）、钙调神经磷酸酶和甘油醛-3-磷酸脱氢酶（GAPDH）基因表达水平。结果以中位值为界值，将患者分为低表达组和高表达组，metastin和AXOR 12基因表达水平具有良好的一致性（kappa系数为0.73），而metastin/AXOR 12信号系统基因表达与DSCR 1 -4基因表达无明显相关性。单因素考克斯回归分析显示，metastin低表达和AXOR 12低表达患者的预后显著差于metastin高表达和AXOR 12高表达患者（p = 0.04和0.018）。metastin和AXOR 12基因表达的组合也对患者预后有显著影响（p = 0.045）。DSCR 1 -1、DSCR 1 -4和calcineurin基因表达对预后无明显影响。结论metastin/AXOR 12信号通路抑制卵巢上皮性癌侵袭表型的确切机制尚不清楚。在唐氏综合征中复制的基因如DSCR 1可能在上皮性卵巢癌的肿瘤发生中不起重要作用。
UNLABELLED 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. PATIENTS AND 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. CONCLUSION 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.