脓毒症患者发生急性肺损伤的机制和生物标记物研究

Study on the Mechanism and Biomarkers of Acute Lung Injury in Patients with Sepsis

目的探索脓毒症患者发生急性肺损伤的发病机制和生物标记物。方法利用R语言在GEO数据库中筛选脓毒症和脓毒症合并急性肺损伤患者两组转录组数据集的差异基因,利用String数据库构建差异基因蛋白-蛋白相互作用网络,利用Cytoscape软件鉴定枢纽基因,利用R语言分析枢纽基因在两组数据集mRNA的相对表达和表达相关性;利用miRTarBase数据库和NetworkAnalys网站构建miRNA-gene网络,筛选与枢纽基因作用的miRNA,利用CIBERSORTx网站对两组数据集进行免疫细胞浸润评估,利用CTD数据库搜索与脓毒症合并急性肺损伤相关的生物标记物作用的分子化合物,以预测脓毒症合并急性肺损伤的治疗药物。结果共鉴定出差异基因12个,其中3个表达上调,9个表达下调;脓毒症患者发生急性肺损伤机制与细胞周期缩短、细胞凋亡增加、细胞铁死亡增加相关;枢纽miRNA miR-335-5p和枢纽基因CDKN1A可能是脓毒症合并急性肺损伤与发病机制相关的重要生物标记物和靶向治疗标记物,共有687种分子化合物与CDKN1A作用,发挥上调其表达的作用。结论miR-335-5p和CDKN1A可能是脓毒症合并急性肺损伤潜在的与发病机制相关的重要生物标记物。

Objective To explore the pathogenesis and biomarkers of acute lung injury in patients with sepsis.Methods The GEO database was used to screen the differential genes in the transcriptome datasets of sepsis and sepsis with acute lung injury using R language;the differential gene protein-protein interaction network was constructed using the String database;the key genes were identified using Cytoscape software;R language was used to analyze the relative expression and expression correlation of hub gene mRNA in the two data sets;the miRNA-gene network was constructed using the miRTarBase database and the NetworkAnalys website to screen the miRNAs that interact with the hub genes.The CIBERSORTx website was used to evaluate the immune cell infiltration of the two sets of data sets.The CTD database was used to search for molecular compounds related to biomarkers associated with sepsis complicated with acute lung injury to predict the therapeutic drugs for sepsis complicated with acute lung injury.Results A total of 12 differential genes were identified,of which 3 genes were up-regulated and 9 genes were down-regulated;the mechanism of acute lung injury in patients with sepsis was related to shortened cell cycle,increased apoptosis,and increased ferroptosis;the hub miRNA miR-335-5p and the hub gene CDKN1A might be important biomarkers and targeted therapeutic markers related to the pathogenesis of sepsis complicated with acute lung injury.A total of 687 molecular compounds interacted with CDKN1A and played a role in up-regulating its expression.Conclusion miR-335-5p and CDKN1A may be potentially important biomarkers related to the pathogenesis of sepsis patients with acute lung injury.