Abstract 12875: Multi-Omics Analysis Strategy is a Promising Approach for Global Identification of New Biomarkers Evaluating Disease Severity of Patients With Dilated Cardiomyopathy
Introduction: Dilated cardiomyopathy (DCM) is an intractable disease and no radical treatment other than cardiac transplantation has been available until today. Because the number of donor heart is limited in Japan, implantation of left ventricular assist device (LVAD) is increasing. Patients can be weaned from LVAD, but no explicit criterion for weaning has been established.
Aim: Discovery of novel biomarkers for evaluating severity/recovery of the DCM and biochemical status of the cardiomyocytes.
Methods: Multi-omics analyses were performed with left ventricular tissues from heart transplant recipients or autopsy cases with idiopathic DCM and dilated phase of HCM (n=19), and compared with non-heart disease controls (n=8). Proteomic analysis was carried out with a Triple TOF5600 mass spectrometer and quantitatively compared using a 2DICAL software. Transcriptomic and epigenomic (DNA methylation) analysis were performed with Agilent DNA Microarray 44K and Infinium Methylation450 BeadChip kits.
Results: 167 proteins showed significant alterations in DCM; proteins associated with cell adhesion, remodeling, and ER stress increased, while those with Ca or energy metabolism decreased. 394 mRNAs showed over 3-fold change in DCM; ANP, BNP, and extracellular matrix mRNAs increased, while expression of myocardial contraction-related genes decreased. 7742 DNA methylation probes showed more than 20% change in DCM; DNA methylation levels were altered in the genes of inflammation, integrin, and TGF-beta signaling pathways. From the genes showing significant changes, we selected and narrowed down the candidate genes based on the correlation with echocardiographic parameters, in addition to their functions, dynamic range, and heart specific expression. Tentatively, 12 candidates for biomarkers have been selected, in addition to reported genes such as periostin and tenascin C, and are being validated by measuring their tissue mRNA and protein levels.
Conclusions: Multi-omics analysis of the left ventricular tissue of DCM provides a number of biomarker candidates. From these candidates, we will be able to identify novel biomarkers estimating the recovery of cardiac function and probability of weaning from LVAD.
Author Disclosures: N. Minamino: None. M. Nishigori: None. H. Yagi: None. S. Muto: None. O. Seguchi: None. T. Osaki: None. A. Mochizuki: None. K. Sasaki: None. M. Asakura: None. Y. Ikeda: None. H. Ishibashi-Ueda: None. Y. Kanai: None. K. Matsumoto: None. T. Nakatani: None.
- © 2014 by American Heart Association, Inc.