The Blood Cell Research Group, Department of Medical Biochemistry. Oslo University Hospital. Ullevål, Norway.
College of Technology, Zayed University, Abu Dhabi, UAE.
Shock. 2023 Oct 1;60(4):503-516. doi: 10.1097/SHK.0000000000002192. Epub 2023 Aug 9.
This study investigated the temporal dynamics of childhood sepsis by analyzing gene expression changes associated with proinflammatory processes. Five datasets, including four meningococcal sepsis shock (MSS) datasets (two temporal and two longitudinal) and one polymicrobial sepsis dataset, were selected to track temporal changes in gene expression. Hierarchical clustering revealed three temporal phases: early, intermediate, and late, providing a framework for understanding sepsis progression. Principal component analysis supported the identification of gene expression trajectories. Differential gene analysis highlighted consistent upregulation of vascular endothelial growth factor A (VEGF-A) and nuclear factor κB1 (NFKB1), genes involved in inflammation, across the sepsis datasets. NFKB1 gene expression also showed temporal changes in the MSS datasets. In the postmortem dataset comparing MSS cases to controls, VEGF-A was upregulated and VEGF-B downregulated. Renal tissue exhibited higher VEGF-A expression compared with other tissues. Similar VEGF-A upregulation and VEGF-B downregulation patterns were observed in the cross-sectional MSS datasets and the polymicrobial sepsis dataset. Hexagonal plots confirmed VEGF-R (VEGF receptor)-VEGF-R2 signaling pathway enrichment in the MSS cross-sectional studies. The polymicrobial sepsis dataset also showed enrichment of the VEGF pathway in septic shock day 3 and sepsis day 3 samples compared with controls. These findings provide unique insights into the dynamic nature of sepsis from a transcriptomic perspective and suggest potential implications for biomarker development. Future research should focus on larger-scale temporal transcriptomic studies with appropriate control groups and validate the identified gene combination as a potential biomarker panel for sepsis.
本研究通过分析与促炎过程相关的基因表达变化，研究了儿童脓毒症的时间动态。选择了五个数据集，包括四个脑膜炎球菌脓毒症休克（MSS）数据集（两个时间和两个纵向）和一个多微生物脓毒症数据集，以跟踪基因表达的时间变化。层次聚类显示了三个时间阶段：早期、中期和晚期，为了解脓毒症的进展提供了一个框架。主成分分析支持鉴定基因表达轨迹。差异基因分析突出了血管内皮生长因子 A（VEGF-A）和核因子κB1（NFKB1）的一致上调，这些基因参与炎症，在脓毒症数据集之间。NFKB1 基因表达在 MSS 数据集也显示出时间变化。在比较 MSS 病例和对照的尸检数据集中，VEGF-A 上调，VEGF-B 下调。与其他组织相比，肾脏组织表现出更高的 VEGF-A 表达。在横向 MSS 数据集和多微生物脓毒症数据集中观察到类似的 VEGF-A 上调和 VEGF-B 下调模式。六边形图证实了在 MSS 横向研究中 VEGF-R（VEGF 受体）-VEGF-R2 信号通路的富集。与对照相比，多微生物脓毒症数据集还显示脓毒性休克第 3 天和脓毒症第 3 天样本中 VEGF 途径的富集。这些发现从转录组学的角度提供了对脓毒症动态性质的独特见解，并暗示了潜在的生物标志物开发意义。未来的研究应侧重于具有适当对照组的更大规模的时间转录组学研究，并验证所鉴定的基因组合是否可作为脓毒症的潜在生物标志物组合。
