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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Molecular Innate Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1470842
This article is part of the Research Topic Application of Multi-omics Analyses in Revealing the Role of Mitochondrial Gene Defects in Disease Progression View all 11 articles

Identification of Key Biomarkers and Therapeutic Targets in Sepsis Through Coagulation-Related Gene Expression and Immune Pathway Analysis

Provisionally accepted
Jing Ge Jing Ge 1*Qijie Deng Qijie Deng 2*Rui Zhou Rui Zhou 1,3*Lushan Xiao Lushan Xiao 1Yahui Hu Yahui Hu 1*Zemao Zheng Zemao Zheng 1*
  • 1 Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China
  • 2 The First Clinical Medical School, Southern Medical University, Guangzhou, China
  • 3 Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, China

The final, formatted version of the article will be published soon.

    Sepsis, characterized by a widespread and dysregulated immune response to infection leading to organ dysfunction, presents significant challenges in diagnosis and treatment.In this study, we investigated 203 coagulation-related genes in sepsis patients to explore their roles in the disease. Through differential gene expression analysis, we identified 20 genes with altered expression patterns. Subsequent correlation analysis, visualized through circos plots and heatmaps, revealed significant relationships among these genes.Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that these genes are involved in immune response activation, coagulation, and immune receptor activity. Disease Ontology (DO) enrichment analysis further linked these genes to autoimmune hemolytic anemia and tumor-related signaling pathways. Additionally, the CIBERSORT analysis highlighted differences in immune cell composition in sepsis patients, revealing an increase in neutrophils and monocytes and a decrease in inactive NK cells, CD8 T cells, and B cells. We employed machine learning techniques, including random forest and SVM, to construct a diagnostic model, identifying FCER1G and FYN as key biomarkers.These biomarkers were validated through their expression levels and ROC curve analysis in an independent validation cohort, demonstrating strong diagnostic potential.Single-cell analysis from the GSE167363 dataset further confirmed the distinct expression profiles of these genes across various cell types, with FCER1G predominantly expressed in monocytes, NK cells, and platelets, and FYN in CD4+ T cells and NK cells. Enrichment analysis via GSEA and ssGSEA revealed that these genes are involved in critical pathways, including intestinal immune networks, fatty acid synthesis, and antigen processing. In conclusion, our comprehensive analysis identifies FCER1G and FYN as promising biomarkers for sepsis, providing valuable insights into the molecular mechanisms of this complex condition. These findings offer new avenues for the development of targeted diagnostic and therapeutic strategies in sepsis management.

    Keywords: Sepsis, coagulation-related genes, immune response, FCER1G, Fyn

    Received: 26 Jul 2024; Accepted: 09 Sep 2024.

    Copyright: © 2024 Ge, Deng, Zhou, Xiao, Hu and Zheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Jing Ge, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, China
    Qijie Deng, The First Clinical Medical School, Southern Medical University, Guangzhou, China
    Rui Zhou, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, China
    Yahui Hu, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, China
    Zemao Zheng, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.