Identification of platelets related THBS1 as a critical gene in sepsis related thrombocytopenia via an integrated bioinformatic analysis

Abstract

Abstract Objective To explore the role of platelet related differentially expressed genes (plt-DEGs) THBS1 in sepsis through integrated bioinformatics analyses and in vivo mouse model. Methods Four GEO derived datasets and platelet related genes were downloaded and intersection was performed to obtain the plt-DEGs in sepsis, followed by GO and KEGG analysis, PPI network, prognostic model establishment and immune cell infiltration analyses. Finally, an LPS-challenged mouse model was established for THBS1 quantification. Results A total of 85 plt-DEGs were obtained, including 56 up- and 29 down-regulated plt-DEGs. Among them, 16 genes showed a significant correlation with survival statue and 10 genes, including PLA2G4A, GNAQ, PIK3CB, LHFPL2, SCCPDH, PRKCD, VEGFA, CCNA2, PRKDC and SLC9A3R1, were found with prognostic prediction ability in sepsis. Moreover, these 10 genes were found correlated with the immune cell infiltration and 9 genes except SLC9A3R1 showed upregulated trend in sepsis. Significantly decreased level of THBS1 was found in LPS-challenged mice and THBS1 was found to be involved in platelet degranulation, response to drug and activation of MAPK activity Conclusions plt-DEGs was found correlated with survival statue, immune cell infiltration and could be used as prognostic marker in Sepsis. Plt-DEG THBS1 could be further studied sepsis thrombocytopenia.