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miR-200a和E-钙黏蛋白在卵巢上皮性癌中的双相表达模式及其与临床病理特征的相关性。

The biphasic expression pattern of miR-200a and E-cadherin in epithelial ovarian cancer and its correlation with clinicopathological features.

作者信息

Xu Shaohua, Xu Peizhen, Wu Wei, Ou Yangjun, Xu Juan, Zhang Guanghua, Li Jinping, Xu Guofeng

机构信息

Department of Biomedical Science, Mercer University School of Medicine, Savanna, GA 31410, USA; Changzhou Maternal and Child Health Hospital Affiliated to Nanjing Medical University, Changzhou 213000, China.

出版信息

Curr Pharm Des. 2014;20(11):1888-95. doi: 10.2174/13816128113199990523.

Abstract

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.

摘要

上皮性卵巢癌(EOC)是妇科恶性肿瘤中导致死亡的主要原因。尽管在改善早期检测和优化化疗方案方面付出了巨大努力,但晚期卵巢癌患者的5年生存率仅为30%。这种疾病的高死亡率归因于超过70%的卵巢癌病例诊断较晚。一类小的非编码RNA,即微小RNA,被发现可在转录后水平调节基因表达。部分(而非全部)数据表明,miR-200家族在多种恶性肿瘤中表达失调。在本研究中,我们证明与良性上皮性卵巢囊肿和正常卵巢组织相比,miR-200a和E-钙黏蛋白在EOC中显著上调。然而,对研究对象的进一步分层显示,与早期(FIGO I+II)和1至2级组相比,miR-200a的表达水平在晚期(FIGO III+V)和3级组中显著下调。同样,与无淋巴结转移组相比,在有淋巴结转移的病例中观察到相对较低水平的miR-200a。E-钙黏蛋白在正常卵巢组织中未表达,在良性上皮性卵巢囊肿中经常表达,而在晚期卵巢癌中表达缺失或水平较低。在EOC中,miR-200a与E-钙黏蛋白之间存在显著正相关。这种双相表达模式表明,miR-200a水平可能作为EOC早期检测的新型生物标志物,并且miR-200a和E-钙黏蛋白是开发抗卵巢癌新治疗模式的候选靶点。

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