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

IF 0.7 4区医学

European Journal of Inflammation Pub Date : 2023-09-23 DOI:10.1177/1721727x231202661

Yan Ma, Shichao Shan, Cheng Luo, Jianlan Mo, Zhaokun Hu, Ren Jing

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引用次数: 0

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.

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通过微阵列技术鉴定非存活败血症患者的潜在生物标志物:一项基于GEO数据集的研究

背景:脓毒症的机制，特别是非幸存者尚未确定。目的:鉴定与非幸存者脓毒症(NSS)相关的关键基因并分析其分子机制。方法:从GEO数据库中获取原始数据，筛选恭顺表达基因(DEGs)。使用GO和KEGG分析分析DEGs的功能注释。对枢纽基因进行了蛋白-蛋白相互作用(PPI)网络和相关分析。此外，通过免疫组织化学和免疫印迹技术，在脂多糖(LPS)诱导的脓毒症小鼠中证实了hub基因。结果:在NSS患者和健康志愿者之间获得了188个deg和32个hub基因。其中，研究了STAT1、ISG15、HERC1、EIF2AK2、RPL27、LY6E、IFI44L、XAF1、RSAD2、HERC6等前10位枢纽基因，通过受体操作者特征曲线分析预测败血症。这些中心基因在翻译、病毒应答和抑制线粒体去极化等生物医学过程中具有丰富的正向调控作用;包括线粒体内膜在内的细胞成分;含连接酶活性等的分子功能。这些中心基因也在甲型流感感染和白细胞跨内皮迁移中富集。这些枢纽基因的表达与NSS的诊断有较好的相关性，如HERC6 (AUC = 0.9753, p = 0.0007)、RPL27 (AUC = 0.9691, p = 0.0008)、ISG15 (AUC = 0.9630, p = 0.0009)、STAT1 (AUC = 0.9383, p = 0.0017)、HERC1 (AUC = 0.9259, p = 0.0023)和XAF1 (AUC = 0.9259, p = 0.0023)。此外，与对照组相比，20 mg/kg LPS可上调肺组织中ISG15、RPL27、LY6E和HERC6的表达。结论:共鉴定出188个DEGs和10个hub基因与NSS相关，其中以肺中表达的ISG15、RPL27、LY6E和HERC6基因最为易感。

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来源期刊

European Journal of Inflammation Medicine-Immunology and Allergy

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期刊介绍： European Journal of Inflammation is a multidisciplinary, peer-reviewed, open access journal covering a wide range of topics in inflammation, including immunology, pathology, pharmacology and related general experimental and clinical research.