Pan Guitao, Huang Guiming, Deng Ruiming
Department of Oral and Maxillofacial Surgery, Ganzhou People's Hospital, Ganzhou City, Jiangxi Province, China.
Department of Anesthesiology, Ganzhou People's Hospital, Ganzhou City, Jiangxi Province, China.
Clinics (Sao Paulo). 2025 Aug 6;80:100738. doi: 10.1016/j.clinsp.2025.100738.
This study explored the effect of Lactate Metabolism-Related Genes (LMRGs) in the diagnosis and prognosis of Sepsis.
599 LMRGs were gained via the Molecular Signatures and GeneCards databases. Next, the authorssifted out Differently Expressed LMRGs (DE-S-LMRGs) through differential expression analysis, Protein-Protein Interactions (PPI) networks, and Weighted Gene Co-expression Network Analysis (WGCNA). Then, DE-S-LMRGs were subjected to Least-Absolute Shrinkage and Selection Operator (LASSO), gene expression patterns, Receiver Operating Characteristic (ROC), and Kaplan-Meier (K-M) survival analyses for obtaining diagnostic genes. Subsequently, the authorsyielded independent factors via univariate and multivariate COX analyses. The diagnostic genes expression levels, immune cell infiltration, immune checkpoint, Human Leukocyte Antigen (HLA) molecules, and K-M survival curves between the clusters were compared. Finally, the authorsapplied quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) for verifying the expression of diagnostic genes in the light of normal and Sepsis samples.
Four diagnostic genes (APRT, ARG1, UMPS, and LDHB) were identified, which were mainly concentrated in energy metabolism-related functions and immune-related pathways. In addition, age and ARG1 were selected as independent prognostic factors. The two clusters of GSE65682 datasets show significant differences in the expression, immune cells, immune checkpoints, HLA molecules, and survivability of the four diagnostic genes. qRT-PCR revealed that the expression levels of four diagnostic genes were congruent with the results of bioinformatics analysis.
APRT, ARG1, UMPS, and LDHB might be new ideas for studies related to the diagnosis and treatment of Sepsis.
本研究探讨乳酸代谢相关基因（LMRGs）在脓毒症诊断和预后中的作用。
通过分子特征数据库和基因卡片数据库获取599个LMRGs。接下来，作者通过差异表达分析、蛋白质-蛋白质相互作用（PPI）网络和加权基因共表达网络分析（WGCNA）筛选出差异表达的LMRGs（DE-S-LMRGs）。然后，对DE-S-LMRGs进行最小绝对收缩和选择算子（LASSO）、基因表达模式、受试者工作特征（ROC）和Kaplan-Meier（K-M）生存分析以获得诊断基因。随后，作者通过单变量和多变量COX分析得出独立因素。比较各簇之间诊断基因的表达水平、免疫细胞浸润、免疫检查点、人类白细胞抗原（HLA）分子和K-M生存曲线。最后，作者应用定量实时聚合酶链反应（qRT-PCR）根据正常样本和脓毒症样本验证诊断基因的表达。
鉴定出四个诊断基因（APRT、ARG1、UMPS和LDHB），它们主要集中在能量代谢相关功能和免疫相关途径中。此外，年龄和ARG1被选为独立的预后因素。GSE65682数据集的两个簇在四个诊断基因的表达、免疫细胞、免疫检查点、HLA分子和生存能力方面存在显著差异。qRT-PCR显示四个诊断基因的表达水平与生物信息学分析结果一致。
APRT、ARG1、UMPS和LDHB可能为脓毒症诊断和治疗相关研究提供新思路。
