铁死亡相关基因在儿童脓毒症中的诊断和预测价值。
Diagnostic and Predictive Values of Ferroptosis-Related Genes in Child Sepsis.
机构信息
Department of Infectious Diseases, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China.
出版信息
Front Immunol. 2022 Jun 30;13:881914. doi: 10.3389/fimmu.2022.881914. eCollection 2022.
BACKGROUND
Early diagnosis of sepsis in children was essential to reducing mortality. This study aimed to explore the value of ferroptosis-related genes in children with sepsis.
METHODS
We screened the septic children microarray dataset from the GEO database and analyzed the ferroptosis-related differentially expressed genes (DEGs). A functional analysis of ferroptosis-related DEGs was performed. The protein-protein interaction network was used to identify hub genes. We explored the immune landscape of sepsis and controls. The value of hub genes in diagnosing sepsis was tested in the training (GSE26440) and validation sets (GSE13904), and ELISA was used to verify their diagnostic value in children with sepsis in our hospital.
RESULTS
A total of 2,103 DEGs in GSE26440 were obtained, of which ferroptosis-related DEGs were 34. Enrichment analysis showed significant enrichment in the ferroptosis and hypoxia pathways (i.e., HIF-1 pathway). The top three genes (HMOX1, MAPK14, TLR4) were selected as hub genes. Immunological analysis suggested that 10 cell types (i.e., CD8/CD4 T cells) were lower in sepsis. Immune checkpoint-related genes CD274 (PD-L1), HAVCR2 (TIM3), and SIGLEC15 were overexpressed in sepsis. The AUROC for the diagnosis of sepsis for HMOX1 and TLR4 ranged from 0.77 to 0.81, while the AUROC of MAPK14 reached 0.935 and 0.941 in the training and validation sets. Serum ELISA results of HMOX1 and TLR4 showed no significant difference in differentiating sepsis. The AUROC of MAPK14 was 0.877. When the diagnostic threshold was 74.852 ng/ml, the sensitivity and specificity were 0.906 and 0.719, respectively.
CONCLUSION
Ferroptosis-related gene MAPK14 is of considerable value in the early diagnosis of sepsis in children.
背景
早期诊断儿童脓毒症对于降低死亡率至关重要。本研究旨在探讨铁死亡相关基因在儿童脓毒症中的价值。
方法
我们从 GEO 数据库中筛选了脓毒症儿童的微阵列数据集，并分析了铁死亡相关差异表达基因（DEGs）。对铁死亡相关 DEGs 进行了功能分析。使用蛋白质-蛋白质相互作用网络来识别关键基因。我们探讨了脓毒症和对照的免疫景观。在训练集（GSE26440）和验证集（GSE13904）中测试了关键基因在诊断脓毒症中的价值，并使用 ELISA 验证了它们在我院脓毒症患儿中的诊断价值。
结果
在 GSE26440 中获得了 2103 个 DEGs，其中铁死亡相关 DEGs 为 34 个。富集分析显示，铁死亡和缺氧途径（即 HIF-1 途径）存在显著富集。选择前三个基因（HMOX1、MAPK14、TLR4）作为关键基因。免疫分析表明，脓毒症中 10 种细胞类型（即 CD8/CD4 T 细胞）较低。免疫检查点相关基因 CD274（PD-L1）、HAVCR2（TIM3）和 SIGLEC15 在脓毒症中表达上调。HMOX1 和 TLR4 诊断脓毒症的 AUC 范围为 0.77 至 0.81，而 MAPK14 在训练集和验证集的 AUC 分别达到 0.935 和 0.941。HMOX1 和 TLR4 的血清 ELISA 结果在区分脓毒症方面没有显著差异。MAPK14 的 AUC 为 0.877。当诊断阈值为 74.852ng/ml 时，敏感性和特异性分别为 0.906 和 0.719。
结论
铁死亡相关基因 MAPK14 对儿童脓毒症的早期诊断具有重要价值。
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