Prediction of Target Genes for Dilated Cardiomyopathy with Heart Failure Based on Bioinformatical Analysis
- VernacularTitle:基于生物信息学探讨合并心力衰竭的扩张型心肌病靶基因的预测
- Author:
Guo LI
1
;
Qian CHEN
1
;
Hong-wei LI
1
;
Chang GUAN
1
;
Zhi-teng CHEN
1
;
Yu-ling ZHANG
1
;
Jing-feng WANG
1
Author Information
1. Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
- Publication Type:Journal Article
- Keywords:
dilated cardiomyopathy;
heart failure;
GEO;
GSEA;
bioinformatics
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2020;41(3):424-435
- CountryChina
- Language:Chinese
-
Abstract:
【Objective】 To study the differentiate expression genes and regulation signaling pathways related to the occurrence and development of dilated cardiomyopathy with heart failure, we used bioinformatics methods to explore gene chip in gene expression omnibus(GEO) and genes related to dilated cardiomyopathy in online mendelian inheritance in man(OMIM) . 【Methods】 GSE21610 and GSE29919 chip gene sets sequenced by Herz- &Diabeteszentrum NRW laboratory of the University of Bochum, Germany with myocardial biopsy specimens from clinical cases under the platform GPL570 and uploaded to GEO public database were selected to perform our study. Myocardial biopsy specimens from dilated cardiomyopathy with heart failure and normal cardiac function were regarded as the experimental group(14 and 21 cases, respectively) and the control group(12 and 8 cases, respectively). Up-regulated expression genes with the criteria: P < 0.05, were screened in GEO2R with the selected samples of two chips, which were then used to perform kyoto encyclopedia of genes and genomes(KEGG) pathways analysis, gene ontology(GO) function analysis, and protein-protein interaction(PPI) analysis, and the results were displayed through Volcano map, Venn map, Heat map, and Bubble charts with enrichment pathways drawn by R language packages. Meanwhile, KEGG pathways with the criteria: NOM. P < 0.05, and core genes relating to dilated cardiomyopathy with heart failure were performed through gene set enrichment analysis (GSEA). All candidate genes were then intersected with the reported genes in the OMIM, respectively, and clinical significance of these candidate genes was explored in relevant literatures. 【Results】 A total of 173 up-regulated expression genes with P < 0.05, were obtained by GEO2R, which are mainly related to inflammatory signals, cell proliferation and differentiation regulating, and classical apoptotic signaling pathways. These genes were intersected with the 754 reported genes in OMIM, and three reported up-regulated expression genes were obtained: NPPA for diagnosis of heart failure, APOA1 that associates with cytokine action, and COL6A1 that regulates lateral tubular remodeling. 158 and 46 core genes from KEGG pathways with NOM. P < 0.05 were obtained by GSEA, respectively, which were then intersected with the 754 reported genes in OMIM, and two core genes were obtained: PRKCA, enhancing myocardial contractility, and BMP2, promoting the development of heart failure. 【Conclusions】 Based on bioinformatics analysis, we found that the candidate genes PRKCA, BMP2, NPPA, and COL6A1 are likely to be closely related to the occurrence and development of dilated cardiomyopathy with heart failure, which can be used to reveal meaningful therapeutic clues and directions for the clinical treatment of dilated cardiomyopathy with advanced cardiac dysfunction.