Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Special Medical Department, Nanchong Central Hospital, Nanchong, Sichuan, China.
Front Immunol. 2022 Dec 2;13:1028785. doi: 10.3389/fimmu.2022.1028785. eCollection 2022.
Sepsis is a life-threatening disease associated with immunosuppression. Immunosuppression could ultimately increase sepsis mortality. This study aimed to identify the prognostic biomarkers related to immunity in sepsis.
Public datasets of sepsis downloaded from the Gene Expression Omnibus (GEO) database were divided into the discovery cohort and the first validation cohort. We used R software to screen differentially expressed genes (DEGs) and analyzed DEGs' functional enrichment in the discovery dataset. Immune-related genes (IRGs) were filtered from the GeneCards website. A Lasso regression model was used to screen candidate prognostic genes from the intersection of DEGs and IRGs. Then, the candidate prognostic genes with significant differences were identified as prognostic genes in the first validation cohort. We further validated the expression of the prognostic genes in the second validation cohort of 81 septic patients recruited from our hospital. In addition, we used four immune infiltration methods (MCP-counter, ssGSEA, ImmuCellAI, and CIBERSORT) to analyze immune cell composition in sepsis. We also explored the correlation between the prognostic biomarker and immune cells.
First, 140 genes were identified as prognostic-related immune genes from the intersection of DEGs and IRGs. We screened 18 candidate prognostic genes in the discovery cohort with the lasso regression model. Second, in the first validation cohort, we identified 4 genes (CFHR2, FCGR2C, GFI1, and TICAM1) as prognostic immune genes. Subsequently, we found that FCGR2C was the only gene differentially expressed between survivors and non-survivors in 81 septic patients. In the discovery and first validation cohorts, the AUC values of FCGR2C were 0.73 and 0.67, respectively. FCGR2C (AUC=0.84) had more value than SOFA (AUC=0.80) and APACHE II (AUC=0.69) in evaluating the prognosis of septic patients in our recruitment cohort. Moreover, FCGR2C may be closely related to many immune cells and functions, such as B cells, NK cells, neutrophils, cytolytic activity, and inflammatory promotion. Finally, enrichment analysis showed that FCGR2C was enriched in the phagosome signaling pathway.
FCGR2C could be an immune biomarker associated with prognosis, which may be a new direction of immunotherapy to reduce sepsis mortality.
脓毒症是一种危及生命的疾病，与免疫抑制有关。免疫抑制最终可能会增加脓毒症的死亡率。本研究旨在确定与脓毒症相关的免疫预后生物标志物。
从基因表达综合数据库（GEO）下载的脓毒症公共数据集被分为发现队列和第一验证队列。我们使用 R 软件筛选差异表达基因（DEGs），并在发现数据集分析 DEGs 的功能富集。从 GeneCards 网站筛选免疫相关基因（IRGs）。使用 Lasso 回归模型从 DEGs 和 IRGs 的交集筛选候选预后基因。然后，在第一验证队列中确定具有显著差异的候选预后基因作为预后基因。我们进一步验证了 81 例我院脓毒症患者的第二验证队列中预后基因的表达。此外，我们使用四种免疫浸润方法（MCP-counter、ssGSEA、ImmuCellAI 和 CIBERSORT）分析脓毒症中的免疫细胞组成。我们还探讨了预后生物标志物与免疫细胞的相关性。
首先，我们从 DEGs 和 IRGs 的交集中确定了 140 个与预后相关的免疫基因。使用 Lasso 回归模型在发现队列中筛选了 18 个候选预后基因。其次，在第一验证队列中，我们确定了 4 个基因（CFHR2、FCGR2C、GFI1 和 TICAM1）作为预后免疫基因。随后，我们发现，在 81 例脓毒症患者中，FCGR2C 是幸存者和非幸存者之间唯一差异表达的基因。在发现队列和第一验证队列中，FCGR2C 的 AUC 值分别为 0.73 和 0.67。在评估我们招募队列中脓毒症患者的预后时，FCGR2C（AUC=0.84）比 SOFA（AUC=0.80）和 APACHE II（AUC=0.69）更有价值。此外，FCGR2C 可能与许多免疫细胞和功能密切相关，如 B 细胞、NK 细胞、中性粒细胞、细胞溶解活性和炎症促进。最后，富集分析表明，FCGR2C 富集在吞噬体信号通路中。
FCGR2C 可能是一种与预后相关的免疫生物标志物，可能是降低脓毒症死亡率的免疫治疗新方向。
