Experimental validation and identify the characteristics of chromatin modulator and potential candidate drugs for sepsis (Preprint)

Abstract

BACKGROUND Sepsis is a common acute and critical disease, which is a systemic inflammatory response syndrome. More and more evidence shows that chromium regulators (CRs) are involved in the progress of inflammation and sepsis. OBJECTIVE The purpose of this study was to explore the role of CRS in sepsis patients and provide prognostic value METHODS CRs were obtained from previous top level studies. We downloaded four microarrays（GSE11755、GSE12624、GSE28750、GSE48080）from Gene Expression Omnibus (GEO). CRs related genes were extracted for differential analysis, and GO, KEGG, DO analysis was conducted for different CRs. We conduct PPI analysis on different CRs and screen hub genes. We use the ssGSEA algorithm to obtain the relevant immune cells and immune function infiltration matrix, and draw the relevant heat map for correlation analysis and difference analysis between immune cells and immune function. We analyzed the correlation between hub genes, immune cells and immune functions, and screened out the most relevant hub genes (IHGs). Finally, IHGs are used to build models, and nomograms, ROC curves, and calibration charts are drawn to predict IHGs related drugs and related miRNAs and genes, and RT-PCR is used to verify related genes. RESULTS We obtained 69 normal blood samples and 106 sepsis patients' blood samples, and extracted relevant CRS genes. GO analysis shows that CRS gene involves histone modification, peptidyl−lysine modification、chromatin remodeling, etc. KEGG analysis involves cell cycle, Viral carcinogenesis and Hepatocellular carcinoma signal pathways. We identified 10 hub genes, including TP53, EZH2, RNF2, and mapped relevant maps. 10 drugs such as PHA may be useful for the treatment of Sepsis. MiRNAs such as hsa-miR-4281, hsa-miR-4715-5p, hsa-miR-409-5p and TP53, CHD3, CBX4 genes are associated with this disease. RT-PCR results showed that the expression levels of TP53 and CHD3 were significantly reduced, and the expression levels of CBX4 were significantly increased CONCLUSIONS Our study provides new insights into the role of CRS in sepsis, and provides reliable biomarkers to determine the prognosis of sepsis patients.