GSEA enrichment pathways.

Background
Septic shock is a life-threatening condition characterized by a failure of organ systems and a high mortality rate. Cuproptosis is a new form of cell death that is triggered by copper overload. However, the relationship between cuproptosis-related genes and septic shock remains unclear.
Methods
The GSE26440 dataset from the GEO database was used to screen differentially expressed genes (DEGs) between control and septic shock samples. Additionally, hub genes related to the progression of septic shock and cuproptosis were screened by Venn analysis. RT-qPCR was utilized to validate the expression of hub genes in peripheral blood lymphocytes from septic shock patients and healthy controls. Next, functional analysis and immune cells infiltration were performed.
Results
SLC31A1 and MTF1 levels were obviously elevated and LIAS and LIPT1 levels were downregulated in septic shock samples, compared to normal controls. The diagnostic values of the four genes were confirmed with receiver operating characteristic (ROC) curves. Additionally, SLC31A1 and MTF1 showed a positive correlation with natural killer cells and LIAS and LIPT1 exhibited a positive correlation with CD8+ T cells. Furthermore, compared to low-level groups, MAPK signaling was activated in the high-SLC31A1 level group, VEGF signaling was activated in the high-MTF1 level group and lipoic acid metabolism was activated in high-LIAS and high-LIPT1 level groups.
Conclusion
This study demonstrates that SLC31A1, MTF1, LIAS, and LIPT1 are dysregulated in septic shock samples, and these genes exhibit potential diagnostic efficacy in septic shock, suggesting that these genes may be potential biomarkers for the diagnosis of septic shock.

背景
脓毒性休克（Septic shock）是一种危及生命的病症，以器官系统衰竭为主要特征，且病死率极高。铜死亡（Cuproptosis）是一种由铜过载触发的新型细胞死亡形式。然而，铜死亡相关基因与脓毒性休克之间的关联仍不明确。
方法
本研究从基因表达综合数据库（Gene Expression Omnibus, GEO）中获取GSE26440数据集，用于筛选对照组与脓毒性休克样本间的差异表达基因（DEGs）。此外，通过韦恩分析（Venn analysis）筛选与脓毒性休克进展及铜死亡相关的核心基因（hub genes）。采用实时荧光定量聚合酶链式反应（RT-qPCR）验证核心基因在脓毒性休克患者与健康对照者外周血淋巴细胞中的表达水平。随后，开展功能富集分析与免疫细胞浸润分析。
结果
与正常对照组相比，脓毒性休克样本中SLC31A1与MTF1的表达水平显著升高，而LIAS与LIPT1的表达水平显著下调。通过受试者工作特征（ROC）曲线验证了这4个基因的诊断价值。此外，SLC31A1与MTF1的表达与自然杀伤细胞呈正相关，LIAS与LIPT1的表达与CD8阳性T细胞呈正相关。进一步分析显示，相较于低表达组，高SLC31A1表达组中丝裂原活化蛋白激酶（MAPK）信号通路被激活，高MTF1表达组中血管内皮生长因子（VEGF）信号通路被激活，而高LIAS与高LIPT1表达组中硫辛酸代谢通路被激活。
结论
本研究证实，脓毒性休克样本中SLC31A1、MTF1、LIAS及LIPT1的表达存在失调，且这些基因在脓毒性休克中具有潜在的诊断效能，提示其可作为脓毒性休克诊断的潜在生物标志物。