Skip to main content

ORIGINAL RESEARCH article

Front. Genet.
Sec. Computational Genomics
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1389630

Identification of Apoptosis-Immune-Related Gene Signature and Construction of Diagnostic Model for Sepsis Based on Single-Cell Sequencing and Bulk Transcriptome Analysis

Provisionally accepted
Zhongyi Sun Zhongyi Sun 1Yanan Hu Yanan Hu 1Jiachen Qu Jiachen Qu 1Qiuyue Zhao Qiuyue Zhao 1Han Gao Han Gao 1Zhiyong Peng Zhiyong Peng 2*
  • 1 Zhongnan Hospital, Wuhan University, Wuhan, Hubei Province, China
  • 2 Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China

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

    Introduction: Sepsis leads to multi-organ dysfunction due to disorders of the host response to infections, which makes diagnosis and prognosis challenging. Apoptosis, a classic programmed cell death, contributes to the pathogenesis of various diseases. However, there is much uncertainty about its mechanism in sepsis. Methods: Three sepsis gene expression profiles (GSE65682, GSE13904, and GSE26378) were down-loaded from the Gene Expression Omnibus (GEO) database. Apoptosis-related genes were obtained from the Kyoto Encyclopedia of Genes and Genomes Pathway database. We utilized LASSO regression and SVM-RFE algorithms to identify characteristic genes associated with sepsis. CIBERSORT and single cell sequencing analysis were employed to explore the po-tential relationship between hub genes and immune cell infiltration. The diagnostic capability of hub genes was validated across multiple external datasets. Subsequently, the animal sepsis model was established to assess the expression levels of hub genes in distinct target organs through RT-qPCR and IHC analysis. Results: We identified 11 apoptosis-related genes as characteristic diagnostic markers for sepsis: CASP8, VDAC2, CHMP1A, CHMP5, FASLG, IFNAR1, JAK1, JAK3, STAT4, IRF9, and BCL2. Subsequently, a prognostic model was constructed using LASSO regression with BCL2, FASLG, IRF9 and JAK3 identified as hub genes. Apoptosis-related genes were closely asso-ciated with the immune response during the sepsis process. Furthermore, in the validation datasets, aside from IRF9, other hub genes demonstrated similar expression patterns and diagnostic abilities as observed in GSE65682 dataset. In the mouse model, the expression differences of hub genes between sepsis and control group revealed the potential impacts on sepsis-induced organ injury. Conclusions: The current findings indicated the participant of apoptosis in sepsis, and apoptosis-related differentially expressed genes could be used for diagnosis biomarkers. BCL2, FASLG, IRF9 and JAK3 might be key regulatory genes affecting apoptosis in sepsis. Our findings provided a novel aspect for further exploration of the pathological mechanisms in sepsis.

    Keywords: Apoptosis, bioinformatics, Function analysis, Gene signature, Immune landscape, Sepsis

    Received: 21 Feb 2024; Accepted: 14 May 2024.

    Copyright: © 2024 Sun, Hu, Qu, Zhao, Gao and Peng. 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: Zhiyong Peng, Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 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.