Identification of potential biomarkers for nonsurvivor sepsis patients via microarray technology: A study based on GEO datasets

Abstract

Background: The mechanism of sepsis especially non-survivors has not yet been identified. Objective: To identify the key genes concerned with non-survivor sepsis (NSS) and analyze its molecular mechanism. Methods: The original data were obtained from the GEO database to screen deferentially expressed genes (DEGs). GO and KEGG analysis were performed to analyze the functional annotation of DEGs. The protein-protein interaction (PPI) network and related analysis of hub genes were carried out. Further, hub genes were confirmed in the lipopolysaccharide (LPS)-induced septic mice by western blotting and immunohistochemistry. Results: We obtained 188 DEGs and 32 hub genes between NSS patients and healthy volunteers. Among of them, the top 10 hub genes including STAT1, ISG15, HERC1, EIF2AK2, RPL27, LY6E, IFI44L, XAF1, RSAD2 and HERC6 were studied, which predict sepsis based on receiver operator characteristic curve analysis. These hub genes were enriched in positive regulation of biomedical process including translation, response to virus and suppression of mitochondrial depolarization, etc.; cell component including mitochondrial inner membrane; molecular function containing ligase activity, etc. These hub genes are also enriched in influenza A infection and leukocyte trans-endothelial migration. The expression of these hub genes is better involved in a diagnosis of NSS, such as HERC6 (AUC = 0.9753, p = .0007), RPL27 (AUC = 0.9691, p = .0008), ISG15 (AUC = 0.9630, p = .0009), STAT1 (AUC = 0.9383, p = .0017), HERC1 (AUC = 0.9259, p = .0023), and XAF1 (AUC = 0.9259, p = .0023). Furthermore, 20 mg/kg of LPS injection up-regulated the expression of ISG15, RPL27, LY6E and HERC6 in the lung tissues compared with control mice. Conclusion: These identified 188 DEGs and 10 hub genes were associated with NSS, especially ISG15, RPL27, LY6E and HERC6 genes expressed in the lung as the most vulnerable organ.