Epithelial ovarian cancer (EOC) is the leading cause of death among gynecologic malignancies. Despite great efforts to improve early detection and optimize chemotherapeutic regimens, the 5-year survival rate is only 30% for patients presenting with late-stage ovarian cancer. The high mortality of this disease is due to late diagnosis in over 70% of ovarian cancer cases. A class of small noncoding RNAs, or microRNAs, was found to regulate gene expression at the post-transcriptional level. Some, but not all, of the data indicated that the miR-200 family was dysregulated in a variety of malignancies. In this study, we demonstrated that miR-200a and E-cadherin were significantly upregulated in EOC compared to benign epithelial ovarian cysts and normal ovarian tissues. However, further stratification of the subject indicated that the expression levels of miR-200a were significantly downregulated in late-stage (FIGO III+V) and grade 3 groups compared with early stage (FIGO I+II) and grade 1 to 2 groups. Similarly, relatively low levels of miR-200a were observed in the lymph compared to the node-negative group. E-cadherin expression was found to be absent in normal ovarian tissue and was frequently expressed in benign epithelial ovarian cysts, with absence or low levels observed in late-stage ovarian cancers. There was a significantly positive correlation between miR-200a and E-cadherin in EOC. The biphasic expression pattern suggested that miR-200a levels may serve as novel biomarkers for the early detection of EOC, and miR-200a and E-cadherin are candidate targets for the development of new treatment modalities against ovarian cancer.

译文

上皮性卵巢癌 (EOC) 是妇科恶性肿瘤死亡的主要原因。尽管为改善早期检测和优化化疗方案做出了巨大努力,但对于晚期卵巢癌患者而言,5年生存率仅30%。这种疾病的高死亡率是由于超过70% 例卵巢癌病例的晚期诊断。发现一类小的非编码rna或microrna在转录后水平上调节基因表达。一些 (但不是全部) 数据表明,miR-200家族在各种恶性肿瘤中失调。在这项研究中,我们证明了与良性上皮性卵巢囊肿和正常卵巢组织相比,EOC中的miR-200a和E-cadherin显着上调。然而,对受试者的进一步分层表明,与早期 (FIGO I II) 和1至2级组相比,晚期 (FIGO III V) 和3级组的miR-200a表达水平显着下调。同样,与淋巴结阴性组相比,在淋巴中观察到相对较低的miR-200a水平。发现E-cadherin表达在正常卵巢组织中不存在,并且在良性上皮性卵巢囊肿中经常表达,在晚期卵巢癌中观察到不存在或低水平。EOC中miR-200a与E-cadherin之间存在显着正相关。双相表达模式表明,miR-200a水平可能是早期检测EOC的新型生物标志物,miR-200a和E-钙粘蛋白是开发针对卵巢癌的新治疗方式的候选靶标。

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