Identification of long non-coding RNAs biomarkers for early diagnosis of myocardial infarction from the dysregulated coding-non-coding co-expression network.
Identification of long non-coding RNAs biomarkers for early diagnosis of myocardial infarction from the dysregulated coding-non-coding co-expression network.
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DOI：
10.18632/oncotarget.11999
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发表时间：
2016-11-08
期刊：
影响因子：
--
通讯作者：
Xia H
中科院分区：
文献类型：
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作者：
Sun C;Jiang H;Sun Z;Gui Y;Xia H
长链非编码rna （lncRNAs）最近被证明是各种癌症的新的有希望的诊断或预后生物标志物。然而，lncRNA表达模式及其在心肌梗死（MI）早期诊断中的预测价值尚未得到系统的研究。在我们的研究中，我们对心肌梗死中的lncRNA表达谱进行了全面分析，发现与健康样本相比，心肌梗死中的lncRNA表达模式发生了改变。随后，我们整合了异常lncrna、mrna及其共失调关系，构建了lncRNA-mRNA失调网络（DLMCEN），发现一些mrna在之前的报道中参与了心血管疾病，提示了lncrna失调在心肌梗死发病机制中的功能作用。因此，利用支持向量机（SVM）和遗漏交叉验证（LOOCV），我们从发现队列中开发了9-lncRNA标记（称为9LncSigAMI），该标记可以区分心肌梗死患者和健康样本，准确率为95.96%，灵敏度为93.88%，特异性为98%，并在另一个完全独立的队列中验证了其对心肌梗死早期诊断的预测能力。功能分析表明，9LncSigAMI中的这9个lncRNA生物标志物可能参与心肌固有免疫和炎症反应，其失调可能导致炎症和免疫系统功能障碍，从而导致心肌梗死复发。通过前瞻性验证，我们的工作确定的9LncSigAMI将提供超出其他已知临床参数的额外诊断信息，并增加对心肌梗死发病机制的分子机制的理解。
Long non-coding RNAs (lncRNAs) have recently been shown as novel promising diagnostic or prognostic biomarkers for various cancers. However, lncRNA expression patterns and their predictive value in early diagnosis of myocardial infarction (MI) have not been systematically investigated. In our study, we performed a comprehensive analysis of lncRNA expression profiles in MI and found altered lncRNA expression pattern in MI compared to healthy samples. We then constructed a lncRNA-mRNA dysregulation network (DLMCEN) by integrating aberrant lncRNAs, mRNAs and their co-dysregulation relationships, and found that some of mRNAs were previously reported to be involved in cardiovascular disease, suggesting the functional roles of dysregulated lncRNAs in the pathogenesis of MI. Therefore, using support vector machine (SVM) and leave one out cross-validation (LOOCV), we developed a 9-lncRNA signature (termed 9LncSigAMI) from the discovery cohort which could distinguish MI patients from healthy samples with accuracy of 95.96%, sensitivity of 93.88% and specificity of 98%, and validated its predictive power in early diagnosis of MI in another completely independent cohort. Functional analysis demonstrated that these nine lncRNA biomarkers in the 9LncSigAMI may be involved in myocardial innate immune and inflammatory response, and their deregulation may lead to the dysfunction of the inflammatory and immune system contributing to MI recurrence. With prospective validation, the 9LncSigAMI identified by our work will provide additional diagnostic information beyond other known clinical parameters, and increase the understanding of the molecular mechanism underlying the pathogenesis of MI.