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. 2018 Jan 22;9(1):56.
doi: 10.3390/genes9010056.

Identification of a Common Different Gene Expression Signature in Ischemic Cardiomyopathy

Yana Li  1 , Qiu Jiang  2 , Zhiwen Ding  3 , Guijian Liu  4 , Peng Yu  5 , Guoliang Jiang  6 , Ziqing Yu  7 , Chunjie Yang  8 , Juying Qian  9 , Hong Jiang  10   11 , Yunzeng Zou  12   13
Affiliations

Identification of a Common Different Gene Expression Signature in Ischemic Cardiomyopathy

Yana Li et al. Genes (Basel). .

Abstract

The molecular mechanisms underlying the development of ischemic cardiomyopathy (ICM) remain poorly understood. Gene expression profiling is helpful to discover the molecular changes taking place in ICM. The aim of this study was to identify the genes that are significantly changed during the development of heart failure caused by ICM. The differentially expressed genes (DEGs) were identified from 162 control samples and 227 ICM patients. PANTHER was used to perform gene ontology (GO), and Reactome for pathway enrichment analysis. A protein-protein interaction network was established using STRING and Cytoscape. A further validation was performed by real-time polymerase chain reaction (RT-PCR). A total of 255 common DEGs was found. Gene ontology, pathway enrichment, and protein-protein interaction analysis showed that nucleic acid-binding proteins, enzymes, and transcription factors accounted for a great part of the DEGs, while immune system signaling and cytokine signaling displayed the most significant changes. Furthermore, seven hub genes and nine transcription factors were identified. Interestingly, the top five upregulated DEGs were located on chromosome Y, and four of the top five downregulated DEGs were involved in immune and inflammation signaling. Further, the top DEGs were validated by RT-PCR in human samples. Our study explored the possible molecular mechanisms of heart failure caused by ischemic heart disease.

Keywords: bioinformatical analysis; ischemic cardiomyopathy; microarrays.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) Overall design of the study. (B) Identification of 255 commonly changed differentially expressed genes (DEGs) from four expression profile datasets (GSE5406, GSE26887, GSE42955, and GSE57338) using GEO2R. Different colored areas represent different datasets. The cross areas represent the commonly changed DEGs. Statistically significant DEGs were defined by p < 0.05. GEO: Gene expression omnibus; ICM: Ischemic cardiomyopathy; DEGs: Differentially expressed genes; GO: Gene ontology; PPI: Protein–protein interaction.
Figure 2
Figure 2
Gene ontology (GO) and pathway analysis of DEGs in ischemic cardiomyopathy. (A) Enriched GO terms in the biological process class; (B) Enriched GO terms in the molecular function class; (C) Enriched GO terms in the cellular component class; (D) The proteins of common DEGs were classified according to function; (E) Significantly enriched pathways of common DEGs. ECM: Extracellular matrix protein; UPR: Unfolded protein response; SDCPTM: SRP-dependent co-translational protein targeting to membrane; RCB: Regulation of cholesterol biosynthesis; TLR: Toll-like receptor; SASP: Senescence-associated secretory phenotype.
Figure 3
Figure 3
Protein–protein interaction (PPI) network complex. A total of 167 DEGs (113 upregulated genes and 67 downregulated genes) were filtered into the PPI network. Red nodes suggest upregulated genes and blue node suggest downregulated genes. The node size is proportional to the edge degree. The edge color suggests the significance according to the p value (the brighter the color, the smaller the p value).
Figure 4
Figure 4
Relative expression level of DEGs. (A) EIF1AY, RPS4Y1, DDX3Y, USP9Y, and UTY were significantly upregulated in ICM patients. (B) SERPINA3, MYOT, CD163, FCN3, and S100A8 were significantly downregulated in ICM patients (n = 3) compared to healthy controls (n = 3). * p < 0.05.
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