Department of Anesthesiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China.
Medicine (Baltimore). 2023 Oct 20;102(42):e35154. doi: 10.1097/MD.0000000000035154.
Septic shock often occurs following critically low blood pressure in patients with sepsis, and is accompanied by a high death rate. Although mitophagy is associated with infection and immune responses, its role in septic shock remains unknown. This study screened effective mitophagy-related genes (MRGs) for medical practice and depicted immune infiltration situations in patients with septic shock. Gene expression profiles of GSE131761 from the Gene Expression Omnibus database were compiled for differential analysis, weighted gene co-expression network analysis, and immune infiltration analysis, while other GSE series were used as validation datasets. A series of validation methods were used to verify the robustness of hub genes, while a nomogram and prognosis model were established for medical practice. Six genes were screened via combinations of differentially expressed genes, weighted gene co-expression network analysis, and MRGs. From this, 3 hub genes (MAP1LC3B, ULK1, and CDC37) were chosen for subsequent analysis based on different validation methods. Gene set enrichment analysis showed that leukocyte trans-endothelial migration and the p53 signaling pathway were abnormally activated during septic shock. Immune infiltration analysis indicated that the imbalance of neutrophils and CD4 naive T cells was significantly correlated with septic shock progression. A nomogram was generated based on MAP1LC3B, ULK1, and CDC37, as well as age. The stability of our model was confirmed using a calibration plot. Importantly, patients with septic shock with the 3 highly expressed hub genes displayed worse prognosis than did patients without septic shock. MAP1LC3B, ULK1, and CDC37 are considered hub MRGs in the development of septic shock and could represent promising diagnostic and prognostic biomarkers in blood tissue. The validated hub genes and immune infiltration pattern expand our knowledge on MRG functional mechanisms, which provides guidance and direction for the development of septic shock diagnostic and therapeutic markers.
脓毒性休克常发生于脓毒症患者的严重低血压后,并伴有高死亡率。虽然自噬与感染和免疫反应有关,但它在脓毒性休克中的作用尚不清楚。本研究筛选了有效的自噬相关基因(MRGs),为医学实践提供了参考,并描述了脓毒性休克患者的免疫浸润情况。从基因表达综合数据库(GEO)中收集了 GSE131761 的基因表达谱,进行差异分析、加权基因共表达网络分析和免疫浸润分析,同时使用其他 GEO 系列作为验证数据集。使用一系列验证方法来验证枢纽基因的稳健性,并建立了一个列线图和预后模型,用于医学实践。通过差异表达基因、加权基因共表达网络分析和 MRGs 的组合筛选出了 6 个基因,然后根据不同的验证方法,从这 6 个基因中选择了 3 个枢纽基因(MAP1LC3B、ULK1 和 CDC37)进行后续分析。基因集富集分析表明,在脓毒性休克中,白细胞跨内皮迁移和 p53 信号通路异常激活。免疫浸润分析表明,中性粒细胞和 CD4 幼稚 T 细胞的失衡与脓毒性休克的进展显著相关。根据 MAP1LC3B、ULK1 和 CDC37 以及年龄生成了一个列线图。通过校准图证实了我们模型的稳定性。重要的是,脓毒性休克患者中 3 个高表达的枢纽基因的表达与较差的预后相关,而无脓毒性休克患者的表达则与较好的预后相关。MAP1LC3B、ULK1 和 CDC37 被认为是脓毒性休克发展中的枢纽 MRGs,它们可能代表血液组织中具有前景的诊断和预后生物标志物。验证的枢纽基因和免疫浸润模式扩展了我们对 MRG 功能机制的认识,为脓毒性休克诊断和治疗标志物的开发提供了指导和方向。