Emergency Department, Beijing Sixth Hospital, Beijing, China.
Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Medicine (Baltimore). 2024 Sep 27;103(39):e39867. doi: 10.1097/MD.0000000000039867.
Sepsis, a multifaceted syndrome driven by an imbalanced host response to infection, remains a significant medical challenge. At its core lies the pivotal role of glycolysis, orchestrating immune responses especially in severe sepsis. The intertwined dynamics between glycolysis, sepsis, and immunity, however, have gaps in knowledge with several Crucial genes still shrouded in ambiguity. We harvested transcriptomic profiles from the peripheral blood of 107 septic patients juxtaposed against 29 healthy controls. Delving into this dataset, differential expression analysis shed light on genes distinctly linked to glycolysis in both cohorts. Harnessing the prowess of LASSO regression and SVM-RFE, we isolated Crucial genes, paving the way for a sepsis risk prediction model, subsequently vetted via Calibration and decision curve analysis. Using the CIBERSORT algorithm, we further mapped 22 immune cell subtypes within the septic samples, establishing potential interactions with the delineated Crucial genes. Our efforts unveiled 21 genes intricately tied to glycolysis that exhibited differential expression patterns. Gene set enrichment analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses offered insights, spotlighting pathways predominantly associated with oxidative phosphorylation, PPAR signaling pathway, Glycolysis/Gluconeogenesis and HIF-1 signaling pathway. Among the myriad genes, IER3, DSC2, and PPARG emerged as linchpins, their prominence in sepsis further validated through ROC analytics. These sentinel genes demonstrated profound affiliations with various immune cell facets, bridging the complex terrain of glycolysis, sepsis, and immune responses. In line with our endeavor to "unveil the glycolysis in sepsis," the discovery of IER3, DSC2, and PPARG reinforces their cardinal roles in sepsis pathogenesis. These revelations accentuate the intricate dance between glycolysis and immunological shifts in septic conditions, offering novel avenues for therapeutic interventions.
脓毒症是一种由宿主对感染的反应失衡引起的多方面综合征，仍然是一个重大的医学挑战。其核心是糖酵解的关键作用，特别是在严重脓毒症中协调免疫反应。然而，糖酵解、脓毒症和免疫之间的相互交织的动态存在知识空白，有几个关键基因仍然存在不确定性。我们从 107 名脓毒症患者和 29 名健康对照者的外周血中采集了转录组谱。在深入研究这个数据集时，差异表达分析揭示了两组中与糖酵解明显相关的基因。利用 LASSO 回归和 SVM-RFE 的优势，我们分离出关键基因，为脓毒症风险预测模型铺平了道路，随后通过校准和决策曲线分析进行了验证。使用 CIBERSORT 算法，我们进一步在脓毒症样本中映射了 22 种免疫细胞亚型，建立了与所定义的关键基因的潜在相互作用。我们的努力揭示了 21 个与糖酵解密切相关的基因，它们表现出不同的表达模式。基因集富集分析（GSEA）和京都基因与基因组百科全书（KEGG）通路分析提供了深入的见解，突出了与氧化磷酸化、PPAR 信号通路、糖酵解/糖异生和 HIF-1 信号通路主要相关的途径。在众多基因中，IER3、DSC2 和 PPARG 是关键基因，通过 ROC 分析进一步验证了它们在脓毒症中的重要性。这些哨兵基因与各种免疫细胞方面有着深刻的关联，架起了糖酵解、脓毒症和免疫反应之间复杂的桥梁。与我们“揭示脓毒症中的糖酵解”的努力一致，IER3、DSC2 和 PPARG 的发现强调了它们在脓毒症发病机制中的核心作用。这些发现突出了糖酵解与脓毒症中免疫变化之间的复杂关系，为治疗干预提供了新的途径。
