Identifying crucial biomarkers in peripheral blood of schizophrenia and screening therapeutic agents by comprehensive bioinformatics analysis

Abstract

Schizophrenia (SCZ) is a sophisticated neurodevelopmental disorder, but the mechanisms remain ambiguous. Thus, we analyzed the transcriptomic datasets to investigate the molecular mechanisms of SCZ to pinpoint novel biomarkers and suggest treatment agents. Four peripheral blood datasets were retrieved from the Gene Expression Omnibus (GEO) database, altogether 27 robust Differentially Expressed Genes (DEGs) were ascertained by robust rank aggregation (RRA) methodology. Enrichment analysis, which performed by Enrichr platform, demonstrated that DEGs are predominantly engaged in immune and inflammatory. Protein-protein interaction (PPI) network was constructed by STRING then visualized by Cytoscape. Hub genes identified by cytohubba plug-in were CXCL2, TLR9, SLPI, LY96, G0S2, EGR2, SELENBP1, NDUFA4, GNLY, CCL22. CIBERSORT algorithm was applied to evaluate the situation of immune infiltration, which revealed differences in T-cell CD8, T-cell CD4 memory resting and macrophage M0. The NetworkAnalyst platform was adopted to detect transcription factors (TFs), microRNAs (miRNAs), diseases and chemicals that interact with DEGs, while drugs interacted with DEGs were detected by Enrichr. TFs such as FOXC1, GATA2, NFIC, USF2, E2F1, miRNAs like mir-16-5p, mir-1-3p, mir-124-3p, mir-155-5p, mir-27a-3p are essential in the regulation of DEGs. mir-367-SMAD7-EGR1, mir-367-SMAD7-ARNT, mir-21-SMAD7-EGR1 may be promising biomarkers for SCZ. DEGs were intimately associated with Myocardial Ischemia, Inflammation, Reperfusion Injury. Chemicals such as VPA, cyclosporine, Aflatoxin B1, arsenic trioxide, drugs like diphenylpyraline, trimethoprim, 4-Aminobenzohydrazide, lanatoside C, may have significant implications for treatment of SCZ. These results would shed light on the molecular mechanisms of SCZ and suggest promising diagnostic biomarkers in peripheral blood and therapeutic tactics.

Keywords: Differentially expressed gene; MicroRNA; Robust rank aggregation; Schizophrenia; Therapy; Transcription factor.