Potential Genes and Mechanisms Linking Intracerebral Hemorrhage and Depression: A Bioinformatics-Based Study

Abstract

Cuihua Zou,1,2,* Xiaohua Huang,1,2,* Xuequn Lan,1 Xiaorui Huang,1 Yun Feng,1 Jianmin Huang,1 Lanqing Meng,1 Chongdong Jian,1 Donghua Zou,3 Jie Wang,4 Xuebin Li1,2 1Department of Neurology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, People’s Republic of China; 2Department of Neurology, Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, People’s Republic of China; 3Department of Neurology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530022, People’s Republic of China; 4Department of Nephrology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie Wang; Xuebin LiThe Affiliated Hospital of Youjiang Medical University for Nationalities, 18 Zhongshan er Road, Baise, Guangxi, 533000, People’s Republic of ChinaEmail [email protected]; [email protected]: The purpose of this study was to investigate the potential pathogenic mechanisms of post-intracerebral hemorrhage depression.Methods: Profiles of gene expression in brain tissue of patients with intracerebral hemorrhage (ICH) or depression were downloaded from the Gene Expression Omnibus (GEO) database. We analyzed differentially expressed genes (DEGs) for the two diseases separately. With these DEGs, we conducted an enrichment analysis based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) as well as cross-talk analysis, then we identified hub bridge genes using integrated bridge landscape analysis.Results: We found 131 DEGs for interaction between ICH and depression. In the enrichment analysis, we found 55 GO terms and KEGG pathways involving interacting genes of ICH and depression, and 10 GO terms and 10 KEGG pathways most significantly related to cross-talk between ICH and depression. In the integrated bridge landscape analysis, we identified 20 hub bridge genes. In further analysis, we found that hub bridge genes HLA-A, HMOX1, and JUN related to endocytosis, cell adhesion, and phagosomes may exert their effects through the dopamine (DA) system and the serotonergic pathway post-ICH depression. HLA-A may play a role in the occurrence and development of ICH and depression through immune mediation and cell adhesion. HMOX1 and JUN may participate in the mechanism by interacting with HLA-A.Conclusion: Through bioinformatics analysis, we identified potential hub bridge genes and pathways related to post-ICH depression. Our study provides references for further research on mechanisms on the pathogenesis of post-ICH depression.Keywords: intracerebral hemorrhage, depression, differentially expressed genes, hub bridge genes

Keywords

• intracerebral hemorrhage
• depression
• differentially expressed genes
• hub bridge genes