MiR-378 as a biomarker for response to anti-angiogenic treatment in ovarian cancer
MiR-378 as a biomarker for response to anti-angiogenic treatment in ovarian cancer
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DOI：
10.1016/j.ygyno.2014.03.564
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发表时间：
2014-06-01
影响因子：
4.7
通讯作者：
Matei, Daniela
中科院分区：
文献类型：
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作者：
Chan, John K;Kiet, Tuyen K.;Matei, Daniela
目标。确定miR-378作为卵巢癌抗血管生成治疗反应的生物标志物的作用。采用qRT-PCR方法分析miR-378在卵巢癌细胞系、人卵巢癌和正常卵巢上皮细胞中的表达。将miR-378基因导入SKOV3细胞，利用基因芯片技术鉴定基因表达异常。利用来自癌症基因组图谱(TCGA)的数据，通过Kaplan-Meier和Cox比例风险分析，将miR-378的表达与接受抗血管生成治疗的患者的无进展生存期(PFS)相关联。与正常卵巢上皮细胞相比，MIR-378在卵巢癌细胞和肿瘤中过表达。在卵巢癌细胞中过表达miR-378改变了与血管生成(alcam、EHD1、ELK3、TLN1)、细胞凋亡(RPN2、HIPK3)和细胞周期调节(SWAP-70、LSM14A、RDX)相关的基因的表达。在TCGA数据集中，在接受贝伐单抗治疗的复发性卵巢癌患者中，miR-378的低表达与高表达与较长的PFS相关(9.2个月与4.2个月；p=0.04)。多因素分析显示，miR-378表达是抗血管生成治疗后PFS的独立预测因素(HR=2.04，95%CI：1.12~3.72；P=0.02)。此外，在接受抗血管生成治疗的患者中，两个miR-378靶基因(alcam和EHD1)的表达水平与PFS相关(高alcam和低alcam分别为9.4个月和4.2个月，p=0.04；低alcam和低EHD1分别为7.9个月和23个月，p<；0.01)。我们的数据表明miR-378在卵巢癌细胞和肿瘤中过表达，而在正常卵巢上皮细胞中不表达。MiR-378及其下游靶点可作为Teo抗血管生成治疗反应的标志物。(C)2014 Elsevier Inc.保留所有权利。
Objective. To determine the role of miR-378 as a biomarker for anti-angiogenic therapy response in ovarian cancer.Methods. Expression of miR-378 was analyzed in ovarian cancer cell lines and human tumors vs. normal ovarian epithelial cells by qRT-PCR. After miR-378 transfection in SKOV3 cells, dysregulated genes were identified using microarray. Data from The Cancer Genome Atlas (TCGA) was utilized to correlate miR-378 expression with progression-free survival (PFS) among patients treated with anti-angiogenic therapy by using Kaplan-Meier and Cox proportional hazards.Results. MiR-378 was overexpressed in ovarian cancer cells and tumors vs. normal ovarian epithelial cells. Overexpressing miR-378 in ovarian cancer cells altered expression of genes associated with angiogenesis (ALCAM, EHD1, ELK3, TLN1), apoptosis (RPN2, HIPK3), and cell cycle regulation (SWAP-70, LSM14A, RDX). In the TCGA dataset, low vs. high miR-378 expression was associated with longer PFS in a subset of patients with recurrent ovarian cancer treated with bevacizumab (9.2 vs. 4.2 months; p = 0.04). On multivariate analysis, miR-378 expression was an independent predictor for PFS after anti-angiogenic treatment (HR = 2.04, 95% Cl: 1.12-3.72; p = 0.02). Furthermore, expression levels of two miR-378 targets (ALCAM and EHD1) were associated with PFS in this subgroup of patients who received anti-angiogenic therapy (9.4 vs. 4.2 months, p = 0.04 for high vs. low ALCAM; 7.9 vs. 23 months, p < 0.01 for low vs. high EHD1).Conclusions. Our data suggest that miR-378 is overexpressed in ovarian cancer cells and tumors vs. normal ovarian epithelial cells. MiR-378 and its downstream targets may serve as markers for response teo anti-angiogenic therapy. (C) 2014 Elsevier Inc. All rights reserved.