Identification of potential hub genes for the diagnosis and therapy of dilated cardiomyopathy with heart failure through bioinformatics analysis

Xinghui Zhuang^1,2†, Mengyue Tian^3†, Liming Li^2,4, Shurong Xu⁵, Meiling Cai⁵, Xiaojie Yang^2,4, Zhihuang Qiu^1,2, Tianci Chai^1,2,6, Liangwan Chen^1,2*

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¹ Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou, China

² Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, China

³ Key Laboratory of Ministry of Education for Gastrointestinal Caner, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China

⁴ Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China

⁵ Department of Nursing, Fujian Medical University Union Hospital, Fuzhou, China

⁶ Department of Anesthesiology, Xinyi People’s Hospital, Xuzhou, China

Global Translational Medicine 2022, 1(1), 104 https://doi.org/10.36922/gtm.v1i1.104

Submitted: 20 May 2022 | Accepted: 16 June 2022 | Published: 28 June 2022

© 2022 by the Authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )

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Abstract

Dilated cardiomyopathy (DCM) is a common cause of heart failure. However, genetic-level treatments are not available for this condition. In this study, we searched for biological markers and therapeutic targets for DCM from a genetic perspective. We chose microarray datasets of idiopathic DCM with heart failure tissues and normal function (NF) heart tissues, which were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were analyzed by the GEO2R tool. Gene ontology (GO) and gene set enrichment analysis were used to analyze the functions of DEGs and the pathways in which they are involved. Next, protein-protein interaction networks were built to filter out the hub genes from DEGs. The expression of hub gene was validated by other GEO datasets. Receiver operating characteristic (ROC) curves were plotted to verify the accuracy of the genetic diagnosis. In the end, the mRNA-miRNA-lncRNA network was built to find potentially correlative genes. Twenty-eight common DEGs in total were screened, and GO analysis showed that DEGs were mainly associated with neutrophil degranulation and activation, regulation of Wnt signaling pathway and the development of cardiac cell and tissue. Five hub genes (asporin [ASPN], osteoglycin [OGN], secreted frizzled-related protein 4 [SFRP4], membrane metalloendopeptidase [MME], and natriuretic peptide gene [NPPA]) were shown to be highly expressed in the validation sets and accurate in distinguish between DCM and NF by ROC curves. miRNA prediction of the hub genes revealed that hsa-mir-28b-5p was associated with SFRP4, ASPN, and MME. All of them may serve as biological diagnostic indicators and provide direction for treatment at the genetic level.

Keywords

Dilated cardiomyopathy

Heart failure

Bioinformatics analysis

Differentially expressed genes

Hub genes

Funding

National Natural Science Foundation of China

Fujian Province Major Science and Technology Program

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Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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