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- 2016
microRNA-151检测用于评价卵巢癌铂类药物疗效的临床价值
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Abstract:
目的:探讨microRNA检测用于评价卵巢癌患者铂类药物疗效的临床价值。方法:研究纳入接受顺铂化疗的初治卵巢癌患者88例,根据ATP-TCA结果分为敏感组(45例)和耐药组(43例)。microRNA微阵列分析2组患者血清microRNA表达的差异,并使用qRT-PCR加以验证。绘制ROC曲线,分析microRNA-151高表达与卵巢癌化疗不敏感现象的关系。体外培养SKOV3细胞并转染pcDNA3.1-microRNA-151或pcDNA3.1空质粒,使用3 μmol/L顺铂处理细胞48 h,计算细胞存活率,同时采用qRT-PCR及Western blot检测microRNA-151对细胞Bcl-2表达的影响。结果:与敏感组患者相比,耐药组患者中有5种microRNA表达上调,5种microRNA表达下调。microRNA-151水平的检测对于评价卵巢癌患者铂类药物疗效有临床价值(AUC=0.719, 95%CI=0.607~0.831),高microRNA-151水平的患者发生对铂类药物不敏感的风险较高。高表达microRNA-151可减弱SKOV3细胞对铂类药物的敏感性,提高Bcl-2的表达(P均<0.05)。结论:检测microRNA-151水平可以评估卵巢癌患者对铂类药物的敏感性。
Aim: To investigate the clinical value of microRNA-151 in evaluating effect of platinum drugs on patients with ovarian cancer.Methods: Eighty-eight ovarian cancer patients treated with platinum drugs were allocated into sensitive group and insensitive group according to the result of ATP-TCA test. MicroRNA microarray was used to detect the change of microRNA expression between two groups and the results was proven by qRT-PCR. The clinical value of detecting microRNA-151 was estimated by ROC curves. Furthermore, SKOV3 cells were cultured in vitro and transfected with pcDNA3.1-microRNA-151 or empty pcDNA3.1. Non-transfected SKOV3 cells and transfected SKOV3 cells were treated with 3 μmol/L cisplatin for 48 h and CCK-8 assay was used to calculate the viability of different cells. Finally, the Bcl-2 expression change induced by microRNA-151 was confirmed by qRT-PCR and Western blot.Results: Compared with sensitive group, in insensitive group,5 kinds of microRNA expression were decreased and 5 were increased.ROC curves supported that microRNA-151 had effectively clinical value to assess the sensitivity of ovarian cancer patients to platinum drugs(AUC=0.719, 95%CI=0.607-0.831). High-expressed microRNA-151 was a risk factor for ovarian cancer patients to induce resistance to platinum drugs; moreover, high-expressed microRNA-151 could induce the resistance of SKOV3 cells to platinum drugs and increase Bcl-2 expression(P<0.05).Conclusion: MicroRNA-151 could be used to evaluate the sensitivity of ovarian cancer patients to platinum drugs