Chen Qi, Zhang ChiYuan, Chen YingHan, Lou Jie, Wang DanBo
Department of Obstetrics & Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang, China.
Aust N Z J Obstet Gynaecol. 2012 Apr;52(2):140-5. doi: 10.1111/j.1479-828X.2011.01405.x. Epub 2012 Jan 25.
Accumulated evidence reveals that abnormally expressed genes in eutopic endometrium of endometriosis play a critical role in the pathogenesis of endometriosis.
Identification of endometriosis-related genes for further revealing the pathogenesis of endometriosis and offering the basis for developing the molecular-targeted diagnosis and therapy of endometriosis.
Forty women with endometriosis and forty control women without endometriosis during their secretory phase were selected for this study. cDNA representational difference analysis (cDNA-RDA) was performed to screen the up-regulated genes in eutopic endometrium samples of endometriosis (n = 10) compared with the controls (n = 10). To validate the results, MAT2A, the most abundantly expressed gene, was selected to detect mRNA and protein levels between eutopic endometrium of endometriosis (n = 40) and controls (n = 40) using immunohistochemistry, real-time fluorescent quantitative PCR and Western blotting.
Ten up-regulated genes were identified in eutopic endometria of endometriosis compared with controls. Among these genes, COX-2, BRAF, NRAS and CFL1 have already been reported to be associated with the endometriosis in previous studies. MAT2A, SEPT9, ATAD3A and CADM2 have been reported to be involved in other diseases but not in endometriosis. NAA15 and CCDC21 have not reported in any diseases. Further study showed that MAT2A protein was localised in both endometrial glandular and stromal cells. Compared with controls, the mRNA and protein levels of MAT2A were significantly higher in eutopic endometrium of endometriosis (P < 0.05).
cDNA-RDA can be used to effectively identify the endometriosis-related genes, which can provide novel experimental data and further understand the pathogenesis of endometriosis.
积累的证据表明,子宫内膜异位症在位内膜中异常表达的基因在子宫内膜异位症的发病机制中起关键作用。
鉴定与子宫内膜异位症相关的基因,以进一步揭示子宫内膜异位症的发病机制,并为开发子宫内膜异位症的分子靶向诊断和治疗提供依据。
本研究选取了40例处于分泌期的子宫内膜异位症患者和40例无子宫内膜异位症的对照女性。采用cDNA代表性差异分析(cDNA-RDA)筛选子宫内膜异位症在位内膜样本(n = 10)与对照样本(n = 10)中上调的基因。为验证结果,选择表达量最高的基因MAT2A,采用免疫组织化学、实时荧光定量PCR和蛋白质免疫印迹法检测子宫内膜异位症在位内膜(n = 40)与对照(n = 40)之间的mRNA和蛋白质水平。
与对照相比,在子宫内膜异位症在位内膜中鉴定出10个上调基因。在这些基因中,COX-2、BRAF、NRAS和CFL1在先前的研究中已被报道与子宫内膜异位症有关。MAT2A、SEPT9、ATAD3A和CADM2已被报道参与其他疾病,但与子宫内膜异位症无关。NAA15和CCDC21尚未在任何疾病中报道。进一步研究表明,MAT2A蛋白定位于子宫内膜腺细胞和间质细胞。与对照相比,子宫内膜异位症在位内膜中MAT2A的mRNA和蛋白质水平显著升高(P < 0.05)。
cDNA-RDA可有效鉴定与子宫内膜异位症相关的基因,为进一步了解子宫内膜异位症的发病机制提供新的实验数据。