miR-631的表达与卵巢上皮性癌预后的关系

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摘要目的：分析微小RNA-631（miR-631）的表达量与卵巢上皮性癌（EOC）患者临床病理特征和预后的关系，并探讨miR-631对EOC细胞迁移的作用及对成瘤体积的影响。方法：从癌症和肿瘤基因图谱（TCGA）数据库中提取570例EOC患者的临床病理特征及相应的miR-631的相对表达量，由X-tile软件计算出miR-631相对表达量的最佳截断值，根据此最佳截断值将患者分为miR-631高表达组和miR-631低表达组，再用Kaplan-Meier曲线和Cox比例风险模型来评估miR-631表达量在EOC患者中的预后价值。挑选miR-631低表达的EOC细胞株A2780、COV504和miR-631高表达的细胞株ES2和SKOV3，分别上调和下调miR-631表达量，观察细胞迁移能力。建立裸鼠EOC模型，分为对照组和miR-631类似物组，观察2组肿瘤体积。结果：Kaplan-Meier分析显示，miR-631低表达组（miR-631相对表达量＜4.78）的EOC患者的总体生存期（OS）较miR-631高表达组（miR-631相对表达量≥4.78）差（HR=0.65，95%CI=0.47～0.89，P=0.008）。单因素和多因素COX回归分析发现miR-631的表达可能是影响EOC患者预后的独立因素（HR=0.72，95%CI=0.54～0.97，P=0.029）。上调miR-631的表达会抑制EOC细胞的迁移，下调miR-631的表达会促进EOC细胞的迁移。在EOC裸鼠模型中，上调miR-631会减小EOC体积。结论：miR-631的低表达可能预示着EOC患者预后较差，上调miR-631可以抑制EOC细胞的迁移，并且可以显著地减小肿瘤体积，可能对EOC有治疗意义。

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	余丹扬
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	段萍

关键词 ：卵巢上皮性癌, miR-631, 预后, 迁移

Abstract：Objective: To explore the data of epithelial ovarian carcinoma (EOC) patients in the Tumor and Cancer Gene Map (TCGA) database by analyzing the relationship between the expression of microRNA-631 (miR-631) and the clinicopathological features and prognosis of EOC patients and to investigate the effect of miR-631 on EOC cell migration and tumor volume. Methods: Clinical pathological features and corresponding microRNA expression date were extracted from TCGA database of 570 patients with EOC. The optimal cutoff value of miR-631 expression was calculated by X-tile software, and based on this optimal cutoff value the patients were grouped. The Kaplan-Meier curve and the Cox proportional hazards model was performed to assess the prognostic value of miR-631 expression in EOC patients. The miR-631 low-expressing EOC cell lines A2780, COV504 and miR-631 high-expressing cell lines ES2 and SKOV3 were selected by up-regulating the expression of miR-631 in low-expressing cell lines and down-regulating the expression in high-expressing cell lines to observe the ability of cell to migrate. The nude mouse EOC model was established and divided as the control group and miR-631 mimic group. The tumor volume of the two groups was observed. Results: Kaplan-Meier analysis showed that the overall survival (OS) of EOC patients with miR-631 low-level expression group (miR-631 expression value<4.78) was higher than that of EOC patients with miR-631 high-level expression group (miR-631 expression value≥4.78) (HR=0.65, 95%CI=0.47-0.89, P=0.008). Univariate and multivariate COX regression analysis revealed that miR-631 expression may be an independent factor influencing the prognosis of patients with EOC (HR=0.72, 95%CI=0.54-0.97, P=0.029). Up-regulation of miR-631 expression inhibits migration of EOC cells, and down-regulation of miR-631 expression promotes migration of EOC cells. Upregulation of miR-631 expression in the EOC nude mouse model reduced EOC tumor formation volume. Conclusion: Low expression of miR-631 may indicate poor prognosis in patients with EOC. Up-regulation of miR-631 can inhibit EOC migration and significantly reduce tumor volume, which may have therapeutic implications for EOC.

Key words： epithelial ovarian cancer miR-631 prognosis migration

收稿日期: 2018-09-25

基金资助:浙江省自然科学基金资助项目（LY16H160054）；浙江省卫生和计划生育委员会项目（2018ZD009）。

通讯作者: 段萍，教授，主任医师，Email：dppddpp@126.com。

作者简介: 余丹扬（1992-），女，浙江温州人，硕士生。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2019/V49/I10/712

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