miR-638 is a new biomarker for outcome prediction of non-small cell lung cancer patients receiving chemotherapy.

miR-638 is a new biomarker for outcome prediction of non-small cell lung cancer patients receiving chemotherapy.
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miR-638是一种新的生物标志物,用于预测接受化疗的非小细胞肺癌患者的预后。

DOI:
10.1038/emm.2015.17
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发表时间:
2015-05-08
影响因子:
12.8
通讯作者:
Wang, Hong
Wang, Hong
中科院分区:
医学2区
文献类型:
--
作者:
Wang, Fang;Lou, Jian-fang;Cao, Yan;Shi, Xin-hui;Wang, Peng;Xu, Jian;Xie, Er-fu;Xu, Ting;Sun, Rui-hong;Rao, Jian-yu;Huang, Pu-wen;Pan, Shi-yang;Wang, Hong

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microRNA(miRNAs)是一类小的非编码RNA,通过切割靶mRNA或抑制其翻译来介导基因表达。它们在包括非小细胞肺癌(NSCLC)在内的几种癌症的肿瘤发生中起关键作用。本研究的目的是探讨miR-638在评估NSCLC患者化疗预后中的临床意义。首先,我们检测了顺铂处理的NSCLC细胞系SPC-A1培养上清中miR-638的表达水平,以及SPC-A1的凋亡率。第二,通过使用携带SPC-A1的裸鼠异种移植模型在顺铂治疗和不治疗的情况下检测血清miR-638表达水平。在临床上,采用实时荧光定量PCR法检测200例NSCLC患者化疗前后血清miR-638水平,分析化疗后miR-638表达模式与临床病理特征的关系。我们的数据有助于证明顺铂以剂量和时间依赖性方式诱导SPC-A1细胞凋亡,并伴随培养上清液中miR-638表达水平的增加。体内数据进一步揭示,顺铂诱导源自小鼠异种移植模型的血清中的miR-638上调,并且在NSCLC患者血清中,化疗后miR-638表达模式与淋巴结转移显著相关。此外,生存分析显示,化疗后miR-638水平升高的患者的生存时间明显长于miR-638水平降低的患者。我们的研究结果表明,血清miR-638水平与NSCLC患者的生存相关,并可能被认为是NSCLC预后的潜在独立预测因子。
MicroRNAs (miRNAs), a class of small non-coding RNAs, mediate gene expression by either cleaving target mRNAs or inhibiting their translation. They have key roles in the tumorigenesis of several cancers, including non-small cell lung cancer (NSCLC). The aim of this study was to investigate the clinical significance of miR-638 in the evaluation of NSCLC patient prognosis in response to chemotherapy. First, we detected miR-638 expression levels in vitro in the culture supernatants of the NSCLC cell line SPC-A1 treated with cisplatin, as well as the apoptosis rates of SPC-A1. Second, serum miR-638 expression levels were detected in vivo by using nude mice xenograft models bearing SPC-A1 with and without cisplatin treatment. In the clinic, the serum miR-638 levels of 200 cases of NSCLC patients before and after chemotherapy were determined by quantitative real-time PCR, and the associations of clinicopathological features with miR-638 expression patterns after chemotherapy were analyzed. Our data helped in demonstrating that cisplatin induced apoptosis of the SPC-A1 cells in a dose- and time-dependent manner accompanied by increased miR-638 expression levels in the culture supernatants. In vivo data further revealed that cisplatin induced miR-638 upregulation in the serum derived from mice xenograft models, and in NSCLC patient sera, miR-638 expression patterns after chemotherapy significantly correlated with lymph node metastasis. Moreover, survival analyses revealed that patients who had increased miR-638 levels after chemotherapy showed significantly longer survival time than those who had decreased miR-638 levels. Our findings suggest that serum miR-638 levels are associated with the survival of NSCLC patients and may be considered a potential independent predictor for NSCLC prognosis.
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发表时间: 2007-04-27
期刊: SCIENCE
影响因子: 56.9
作者:
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