Circulating microRNAs as biomarkers for early detection of diffuse-type gastric cancer using a mouse model.

Circulating microRNAs as biomarkers for early detection of diffuse-type gastric cancer using a mouse model.
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DOI:
10.1038/bjc.2013.30
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发表时间:
2013-03-05
影响因子:
8.8
通讯作者:
Yuasa Y
Yuasa Y
中科院分区:
医学1区
文献类型:
--
作者:
Rotkrua P;Shimada S;Mogushi K;Akiyama Y;Tanaka H;Yuasa Y

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弥漫型胃癌(DGC)表现出快速的疾病进展和不良预后。目前尚无有效的血清生物标志物用于DGC的早期检测。我们已经建立了一个E-cadherin/p53双条件敲除(DCKO)小鼠系,重演人类DGC的形态和分子。在这项研究中,我们试图使用DCKO小鼠鉴定循环microRNA(miRNAs)作为DGC诊断的非侵入性生物标志物。我们进行了miRNA微阵列和定量逆转录-PCR分析的组织和血清样本的DCKO小鼠与DGC和年龄匹配的同窝对照。比较分析表明,小鼠和人类原发性胃癌具有相似的miRNA表达模式。接下来,我们选择了在DCKO小鼠的血清和癌组织中高表达的一些候选miRNAs用于进一步评估。TaqMan定量RT-PCR分析表明,其中四个,miR-103,miR-107,miR-194和miR-210,在早期和晚期DGC荷瘤小鼠血清中与相应对照组相比显著上调。受试者工作特征曲线分析表明,这4种miRNAs能够以较高的敏感性和特异性区分DGC阳性患者和正常患者。这些观察结果表明,这种DGC小鼠模型可用于鉴定血清生物标志物,并且我们发现了可以在早期准确检测DGC的循环miRNA。
Diffuse-type gastric cancer (DGC) exhibits rapid disease progression and a poor prognosis. There are no effective serum biomarkers for early detection of DGC. We have established an E-cadherin/p53 double conditional knockout (DCKO) mouse line that recapitulates human DGC morphologically and molecularly. In this study we tried to identify circulating microRNAs (miRNAs) as non-invasive biomarkers for DGC diagnosis using DCKO mice. We performed miRNA microarray and quantitative reverse transcription–PCR analyses of tissue and serum samples from DCKO mice with DGC and age-matched littermate controls. Comparative analyses showed that mouse and human primary gastric cancers have similar miRNA expression patterns. Next, we selected some candidate miRNAs highly expressed in sera and cancer tissues of DCKO mice for further evaluation. TaqMan quantitative RT–PCR analyses indicated that four of them, miR-103, miR-107, miR-194 and miR-210, were significantly upregulated in sera of both early and advanced-stage DGC-bearing mice compared with in corresponding controls. Receiver-operating characteristic curve analyses demonstrated that these four miRNAs can discriminate DGC-positive cases from normal ones with high sensitivity and specificity. These observations suggest that this mouse model of DGC is useful for identifying serum biomarkers, and we found circulating miRNAs that can accurately detect DGC at an early stage.
DOI: 10.1038/sj.bjc.6605608
发表时间: 2010-03-30
影响因子: 8.8
作者:
通讯作者: --
鉴定血清 microRNA 作为胃癌早期检测的新型非侵入性生物标志物。
DOI: 10.1371/journal.pone.0033608
发表时间: 2012
期刊: PloS one
影响因子: 3.7
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发表时间: 1965-01-01
期刊: ACTA PATHOLOGICA ET MICROBIOLOGICA SCANDINAVICA
影响因子: --
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发表时间: 2008-06-01
影响因子: 6.5
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发表时间: 2012-08-01
影响因子: 6.4
作者:
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