An Robust Rank Aggregation and Least Absolute Shrinkage and Selection Operator Analysis of Novel Gene Signatures in Dilated Cardiomyopathy

Abstract

Objective: Dilated cardiomyopathy (DCM) is a heart disease with high mortality characterized by progressive cardiac dilation and myocardial contractility reduction. The molecular signature of dilated cardiomyopathy remains to be defined. Hence, seeking potential biomarkers and therapeutic of DCM is urgent and necessary. Methods: In this study, we utilized the Robust Rank Aggregation (RRA) method to integrate four eligible DCM microarray datasets from the GEO and identified a set of significant differentially expressed genes (DEGs) between dilated cardiomyopathy and non-heart failure. Moreover, LASSO analysis was carried out to clarify the diagnostic and DCM clinical features of these genes and identify dilated cardiomyopathy derived diagnostic signatures (DCMDDS). Results: A total of 117 DEGs were identified across the four microarrays. Furthermore, GO analysis demonstrated that these DEGs were mainly enriched in the regulation of inflammatory response, the humoral immune response, the regulation of blood pressure and collagen-containing extracellular matrix. In addition, KEGG analysis revealed that DEGs were mainly enriched in diverse infected signaling pathways. Moreover, Gene set enrichment analysis revealed that immune and inflammatory biological processes such as adaptive immune response, cellular response to interferon and cardiac muscle contraction, dilated cardiomyopathy are significantly enriched in DCM. Moreover, Least absolute shrinkage and selection operator (LASSO) analyses of the 18 DCM-related genes developed a 7-gene signature predictive of DCM. This signature included ANKRD1, COL1A1, MYH6, PERELP, PRKACA, CDKN1A, and OMD. Interestingly, five of these seven genes have a correlation with left ventricular ejection fraction (LVEF) in DCM patients. Conclusion: Our present study demonstrated that the signatures could be robust tools for predicting DCM in clinical practice. And may also be potential treatment targets for clinical implication in the future.

Keywords: Least absolute shrinkage and selection operator analysis; PERELP; Robust Rank Aggregation; dilated cardiomyopathy; novel gene signatures.