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六种基于血清的微小RNA作为胃癌潜在的诊断生物标志物

Six Serum-Based miRNAs as Potential Diagnostic Biomarkers for Gastric Cancer.

作者信息

Huang Zebo, Zhu Danxia, Wu Lirong, He Mingfeng, Zhou Xin, Zhang Lan, Zhang Huo, Wang Weiwei, Zhu Jun, Cheng Wenfang, Chen Yan, Fan Yong, Qi Lianwen, Yin Yin, Zhu Wei, Shu Yongqian, Liu Ping

机构信息

Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, China.

出版信息

Cancer Epidemiol Biomarkers Prev. 2017 Feb;26(2):188-196. doi: 10.1158/1055-9965.EPI-16-0607. Epub 2016 Oct 18.

DOI:10.1158/1055-9965.EPI-16-0607
PMID:27756776
Abstract

BACKGROUND

Circulating miRNAs in serum may serve as promising diagnostic biomarkers for patients with gastric cancer.

METHODS

Using qRT-PCR-based Exiqon panel, we identified 58 differentially expressed miRNAs from three gastric cancer pool samples and one normal control (NC) pool in the initial screening phase. Identified miRNAs were further validated in the training (49 gastric cancer vs. 47 NCs) and validation phases (154 gastric cancer vs. 120 NCs) using qRT-PCR. The expression levels of the miRNAs were also determined in tissues, arterial serum, and exosomes.

RESULTS

Consequently, six serum miRNAs (miR10b-5p, miR132-3p, miR185-5p, miR195-5p, miR-20a3p, and miR296-5p) were significantly overexpressed in gastric cancer compared with NCs. The areas under the receiver operating characteristic curve of the six-miRNA panel were 0.764 and 0.702 for the training and validation phases, respectively. miR10b-5p and miR296-5p were significantly upregulated in gastric cancer tissues (n = 188). In addition, patients who did not receive adjuvant chemotherapy with high expression of miR10b-5p or miR296-5p in tissues tended to suffer worse overall survival. Furthermore, the expression levels of miR10b-5p, miR195-5p, miR20a-3p, and miR296-5p were significantly elevated in exosomes from gastric cancer serum samples (n = 30).

CONCLUSIONS

We identified a six-miRNA panel in serum for the detection of gastric cancer.

IMPACT

Our findings provide a novel serum miRNA signature for gastric cancer diagnosis, and will serve as the basis of the application of circulating miRNAs in clinical for the detection of gastric cancer in the future. Cancer Epidemiol Biomarkers Prev; 26(2); 188-96. ©2016 AACR.

摘要

背景

血清中的循环miRNA可能是胃癌患者有前景的诊断生物标志物。

方法

在初始筛选阶段,我们使用基于qRT-PCR的Exiqon检测板,从三个胃癌混合样本和一个正常对照(NC)混合样本中鉴定出58个差异表达的miRNA。使用qRT-PCR在训练阶段(49例胃癌患者与47例NC)和验证阶段(154例胃癌患者与120例NC)对鉴定出的miRNA进行进一步验证。还在组织、动脉血清和外泌体中测定了这些miRNA的表达水平。

结果

因此,与NC相比,六种血清miRNA(miR10b-5p、miR132-3p、miR185-5p、miR195-5p、miR-20a3p和miR296-5p)在胃癌中显著过表达。六种miRNA检测板在训练阶段和验证阶段的受试者操作特征曲线下面积分别为0.764和0.702。miR10b-5p和miR296-5p在胃癌组织(n = 188)中显著上调。此外,组织中miR10b-5p或miR296-5p高表达且未接受辅助化疗的患者总体生存期往往较差。此外,胃癌血清样本(n = 30)的外泌体中miR10b-5p、miR195-5p、miR20a-3p和miR296-5p的表达水平显著升高。

结论

我们在血清中鉴定出一个用于检测胃癌的六种miRNA检测板。

影响

我们的研究结果为胃癌诊断提供了一种新的血清miRNA特征,将作为未来循环miRNA在临床中应用于检测胃癌的基础。癌症流行病学、生物标志物与预防;26(2);188 - 96。©2016美国癌症研究协会。

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