Expression profile of circulating microRNAs as a promising fingerprint for cervical cancer diagnosis and monitoringy

Expression profile of circulating microRNAs as a promising fingerprint for cervical cancer diagnosis and monitoringy
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DOI:
10.3892/mco.2015.560
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发表时间:
2015-07-01
影响因子:
1.2
通讯作者:
Xiang, Yang
Xiang, Yang
中科院分区:
其他
文献类型:
--
作者:
Jia, Wenhui;Wu, Yuanzhe;Xiang, Yang

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为了降低宫颈癌的高发病率和死亡率,迫切需要敏感和特异性的生物标志物来早期检测宫颈癌。我们之前证明了循环microRNAs (miRNAs)与某些类型的人类癌症相关。本研究的目的是研究宫颈癌患者血清mirna谱的改变,以便在相对早期阶段预测宫颈癌。收集了213名宫颈癌患者和158名年龄和种族匹配的对照组的血清样本。通过Solexa测序进行miRNA表达的初步筛选。采用茎环miRNA定量聚合酶链反应(qPCR)方法对单个样品进行差异表达验证,并对样品进行两阶段选择和验证。Solexa测序结果显示,与对照组相比,宫颈癌患者的血清mirna有12个显著上调。逆转录- qpcr分析鉴定出5种血清mirna (miR-21, -29a, -25, -200a和-486-5p)作为宫颈癌生物标志物。受试者工作特征曲线表明,与任何基于单一mirna的检测、鳞状细胞癌抗原或碳水化合物抗原125相比,5个mirna组成的小组构成了更敏感和特异性的诊断测试。更重要的是,miR-29a和miR-200a可能指示肿瘤的组织学分级和进展阶段。因此,从全基因组血清miRNA表达谱中鉴定出的5-miRNA特征可以作为宫颈癌诊断的指纹。
Sensitive and specific biomarkers for the early detection of cervical cancer are urgently required to reduce the high morbidity and mortality of this disease. We previously demonstrated that circulating microRNAs (miRNAs) are correlated with certain types of human cancer. The aim of this study was to investigate the altered profile of serum miRNAs in cervical cancer patients in order to predict cervical cancer at a relative early stage. Serum samples were collected from 213 cervical cancer patients and 158 age-and ethnicity-matched controls. An initial screening of miRNA expression was performed by Solexa sequencing. Differential expression was validated using the stem-loop miRNA quantitative polymerase chain reaction (qPCR) assay in individual samples and the samples were arranged by two-phase selection and validation. The Solexa sequencing results revealed 12 markedly upregulated serum miRNAs in cervical cancer patients compared with controls. The reverse transcription-qPCR analysis identified a profile of 5 serum miRNAs (miR-21, -29a, -25, -200a and -486-5p) as a cervical cancer biomarker. The receiver operating characteristic curves indicated that a panel of 5 miRNAs constitutes a more sensitive and specific diagnostic test compared with any single miRNA-based assay, the squamous cell carcinoma antigen or the carbohydrate antigen 125. More importantly, miR-29a and miR-200a may indicate tumor histological grade and progression stage. Therefore, a 5-miRNA signature identified from genome-wide serum miRNA expression profiling may serve as a fingerprint for cervical cancer diagnosis.