Abstract
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.
Highlights
Myocardial Infarction (MI), commonly known as heart attack, is a serious result of coronary artery disease (CAD) caused by sudden blockage or extremely reduced blood flow in a coronary artery
The Long non-coding RNAs (lncRNAs)-mRNA pairs with a high Pearson correlation coefficient (PCC) (>0.5) were selected as significantly dysregulated lncRNA-mRNA co-expression pairs and were integrated into the dysregulated lncRNA-mRNA coexpression network (DLMCEN), in which there are 1822 edges between 188 mRNAs and 11 lncRNAs (Figure 1A)
The down-regulated expression of lncRNA UCA1 has been observed at the early state of AMI patients [29]
Summary
Myocardial Infarction (MI), commonly known as heart attack, is a serious result of coronary artery disease (CAD) caused by sudden blockage or extremely reduced blood flow in a coronary artery. MI remains the major cause of death and mortality globally, including China [1]. There is a sharply increasing trend in the morbidity of MI in China. Statistics in 2011 suggested that there were about two million cases of MI accounting for 0.87% of cardiovascular disease (CVD)[2], it is estimated by that the number of patients with MI will increase to 23 million by 2030 [3]. Diagnosis identifying subpopulations at high risk of having an infarct is crucial for deciding early tailored treatment to reduce MI mortality. Currently available biomarkers, such as cardiac troponin and creatine kinaseMB (CK-MB), have used to assist with timely diagnosis [4, 5], some novel molecular biomarkers have highlighted their promising potentials and important roles for early management in MI
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