Identification of Hub Diagnostic Biomarkers and Candidate Therapeutic Drugs in Heart Failure

International Journal of General Medicine

关键词: differentially expressed genes;    weighted gene co-expression network analysis;    diagnostic biomarkers;    therapeutic drugs;    heart failure;   

DOI  :  

来源: DOAJ

【 摘 要 】

Yang Guo,1– 4 Bobin Ning,5 Qunhui Zhang,1– 4 Jing Ma,4 Linlin Zhao,1– 4 QiQin Lu,1– 4 Dejun Zhang1,4 1Research Center for High Altitude Medicine, Medical College of Qinghai University, Xining, 810001, People’s Republic of China; 2Key Laboratory of Application and Foundation for High Altitude Medicine Research in Qinghai Province, Medical College of Qinghai University, Xining, 810001, People’s Republic of China; 3Qinghai-Utah Joint Research Key Lab for High Altitude Medicine, Medical College of Qinghai University, Xining, 810001, People’s Republic of China; 4Department of Eco-Environmental Engineering, Qinghai University, Xining, 810016, People’s Republic of China; 5Department of Medicine, The General Hospital of the People’s Liberation Army, Beijing, 100038, People’s Republic of ChinaCorrespondence: Dejun ZhangDepartment of Eco-Environmental Engineering, Qinghai University, Qinghai, 810016, People’s Republic of ChinaEmail [e-mail]: The objective of this study was to identify the potential regulatory mechanisms, diagnostic biomarkers, and therapeutic drugs for heart failure (HF).Methods: Differentially expressed genes (DEGs) between HF and non-failing donors were screened from the GSE57345, GSE5406, and GSE3586 datasets. Database for Annotation Visualization and Integrated Discovery and Metascape were used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses respectively. The GSE57345 dataset was used for weighted gene co-expression network analysis (WGCNA). The intersecting hub genes from the DEGs and WGCNA were identified and verified with the GSE5406 and GSE3586 datasets. The diagnostic value of the hub genes was calculated through receiver operating characteristic analysis and net reclassification index (NRI). Gene set enrichment analysis (GSEA) was used to filter out the signaling pathways associated with the hub genes. SYBYL 2.1 was used for molecular docking of hub targets and potential HF drugs obtained from the connection map.Results: Functional annotation of the DEGs showed enrichment of negative regulation of angiogenesis, endoplasmic reticulum stress response, and heart development. PTN, LUM, ISLR, and ASPN were identified as the hub genes of HF. GSEA showed that the key genes were related to the transforming growth factor-β (TGF-β) and Wnt signaling pathways. Sirolimus, LY-294002, and wortmannin have been confirmed as potential drugs for HF.Conclusion: We identified new hub genes and candidate therapeutic drugs for HF, which are potential diagnostic, therapeutic and prognostic targets and warrant further investigation.Keywords: differentially expressed genes, weighted gene co-expression network analysis, diagnostic biomarkers, therapeutic drugs, heart failure

【 授权许可】

Unknown