# PPI-based screening of hub genes related to sepsis migration/pyroptosis and immune infiltration analysis

**Authors:** Xu Ma, Jianhao Wang, Kun Han, Jinshuai Lu, Zhanzhan Li, Zhanzhan Li, Zhanzhan Li

PMC · DOI: 10.1371/journal.pone.0336982 · PLOS One · 2025-11-18

## TL;DR

This study identifies key genes and miRNA interactions linked to sepsis and immune responses, offering potential biomarkers and therapeutic targets.

## Contribution

Novel identification of sepsis-related hub genes and miRNA interactions through PPI and immune infiltration analysis.

## Key findings

- 3566 differentially expressed genes were identified, with 23 linked to pyroptosis/migration.
- Eight key genes (e.g., TLR2, SIRT1) remained after validation, showing potential as sepsis biomarkers.
- Immune infiltration analysis revealed varied effects on MAPK14 and roles of miRNA dysregulation in sepsis.

## Abstract

Sepsis incidence is rising, but its pathogenesis remains unclear. This study aimed to identify therapeutic targets.

Three GEO datasets (GSE154918, GSE32707, GSE54514) were analyzed after batch correction. Differentially expressed genes (DEGs) were identified, and those related to pyroptosis/migration were cross-analyzed. Functional enrichment (GO/KEGG) and interaction networks (PPI, mRNA-miRNA, mRNA-TF, mRNA-drug) were constructed. External validation used GSE57065, excluding non-significant genes. ROC analysis and immune infiltration were performed.

3566 DEGs (1715 up, 1851 down) were identified, with 23 linked to pyroptosis/migration. Enrichment analysis highlighted roles in cell adhesion, cytokine regulation, and pathways like IL-17, TNF, and Toll-like receptor signaling. mRNA-miRNA interactions for 12 key genes were predicted. After validation, eight key genes remained: TLR2, SIRT1, PTGS2, MAPK14, IL18, ICAM1, CD274, and CASP3. Immune infiltration revealed varied effects on MAPK14.

Key gene alterations may serve as sepsis biomarkers, and miRNA dysregulation could play a critical role in sepsis pathophysiology.

## Linked entities

- **Genes:** TLR2 (toll like receptor 2) [NCBI Gene 7097], SIRT1 (sirtuin 1) [NCBI Gene 23411], PTGS2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 5743], MAPK14 (mitogen-activated protein kinase 14) [NCBI Gene 1432], IL18 (interleukin 18) [NCBI Gene 3606], ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383], CD274 (CD274 molecule) [NCBI Gene 29126], CASP3 (caspase 3) [NCBI Gene 836]

## Full-text entities

- **Genes:** MAPK14 (mitogen-activated protein kinase 14) [NCBI Gene 1432] {aka CSBP, CSBP1, CSBP2, CSPB1, EXIP, Mxi2}, IL18 (interleukin 18) [NCBI Gene 3606] {aka IGIF, IL-18, IL-1g, IL1F4}, ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383] {aka BB2, CD54, P3.58}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, PTGS2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 5743] {aka COX-2, COX2, GRIPGHS, PGG/HS, PGHS-2, PHS-2}, SIRT1 (sirtuin 1) [NCBI Gene 23411] {aka SIR2, SIR2L1, SIR2alpha}, TLR2 (toll like receptor 2) [NCBI Gene 7097] {aka CD282, TIL4}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, F3 (coagulation factor III, tissue factor) [NCBI Gene 2152] {aka CD142, TF, TFA}
- **Diseases:** Sepsis (MESH:D018805)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12626297/full.md

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12626297/full.md

## References

66 references — full list in the complete paper: https://tomesphere.com/paper/PMC12626297/full.md

---
Source: https://tomesphere.com/paper/PMC12626297