Identification of serum microRNAs as novel non-invasive biomarkers for early detection of gastric cancer.

Identification of serum microRNAs as novel non-invasive biomarkers for early detection of gastric cancer.
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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
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
You WC
You WC
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Song MY;Pan KF;Su HJ;Zhang L;Ma JL;Li JY;Yuasa Y;Kang D;Kim YS;You WC

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为了探讨血清mirna作为胃癌早期检测生物标志物的潜力,我们在中国胃癌高发地区临朐开展了一项基于人群的研究。所有受试者均选自两个大型队列研究。采用TaqMan低密度阵列在GC和对照组血清池中鉴定差异mirna,并通过实时定量逆转录-聚合酶链反应在82对GC和对照组和46对发育不良和对照组的个体中进行验证。通过对58例至少有一份胃癌前诊断血清样本的长期随访人群进行回顾性研究,进一步探讨鉴定的血清miRNA表达的时间趋势。miRNA分析结果显示,与对照组相比,GC患者中有16种miRNA显著上调。进一步验证确定了三种血清mirna (miR-221、miR-744和miR-376c)作为GC检测的潜在生物标志物,基于受试者工作特征(ROC)曲线的风险评估分析显示,该小组能够以82.4%的灵敏度和58.8%的特异性区分GC和对照组。MiR-221和miR-376c与GC分化不良呈显著正相关,且MiR-221在不典型增生中的水平高于对照组。此外,回顾性研究显示,这三种miRNA水平在GC发展过程中呈上升趋势(P <0.05),该面板可以在临床GC诊断前5年对收集的血清样本进行分类,总体准确率为79.3%。这些数据表明,血清miR-221、miR-376c和miR-744具有很强的潜力,可以作为早期检测胃癌的新型无创生物标志物。
To investigate the potential of serum miRNAs as biomarkers for early detection of gastric cancer (GC), a population-based study was conducted in Linqu, a high-risk area of GC in China. All subjects were selected from two large cohort studies. Differential miRNAs were identified in serum pools of GC and control using TaqMan low density array, and validated in individual from 82 pairs of GC and control, and 46 pairs of dysplasia and control by real-time quantitative reverse transcription-polymerase chain reaction. The temporal trends of identified serum miRNA expression were further explored in a retrospective study on 58 GC patients who had at least one pre-GC diagnosis serum sample based on the long-term follow-up population. The miRNA profiling results demonstrated that 16 miRNAs were markedly upregulated in GC patients compared to controls. Further validation identified a panel of three serum miRNAs (miR-221, miR-744, and miR-376c) as potential biomarkers for GC detection, and receiver operating characteristic (ROC) curve-based risk assessment analysis revealed that this panel could distinguish GCs from controls with 82.4% sensitivity and 58.8% specificity. MiR-221 and miR-376c demonstrated significantly positive correlation with poor differentiation of GC, and miR-221 displayed higher level in dysplasia than in control. Furthermore, the retrospective study revealed an increasing trend of these three miRNA levels during GC development (P for trend<0.05), and this panel could classify serum samples collected up to 5 years ahead of clinical GC diagnosis with 79.3% overall accuracy. These data suggest that serum miR-221, miR-376c and miR-744 have strong potential as novel non-invasive biomarkers for early detection of GC.
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