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Diagnostic PANoptosis-related genes in acute kidney injury: bioinformatics, machine learning, and validation

Zhen Chen1, Xiaogang Wang1, Yifan Shao1

  • 1Departments of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China.

Annals of Medicine
|September 2, 2025
PubMed
Abstract

Insights

PANoptosis, a cell death process, plays a key role in acute kidney injury (AKI). This study identified specific PANoptosis genes as potential biomarkers for diagnosing AKI and as targets for future therapies.

Area of Science:

  • Molecular Biology
  • Immunology
  • Genetics

Background:

  • Acute kidney injury (AKI) is a critical condition involving rapid kidney function loss and inflammation.
  • PANoptosis, a form of programmed cell death, significantly contributes to AKI's development and progression.
  • Understanding the role of PANoptosis-related genes is crucial for AKI research.

Purpose of the Study:

  • To investigate the diagnostic and therapeutic potential of PANoptosis-related genes in AKI.
  • To identify key PANoptosis genes associated with AKI pathophysiology.
  • To explore the relationship between PANoptosis genes, immune cell infiltration, and potential drug targets in AKI.

Main Methods:

  • Transcriptomic data from kidney biopsies were analyzed to identify differentially expressed genes (DEGs) related to PANoptosis in AKI.
  • Weighted Gene Correlation Network Analysis (WGCNA) was used to identify hub genes.
  • Single-sample Gene Set Enrichment Analysis (ssGSEA) calculated PANoptosis scores and immune cell infiltration.
  • Machine learning algorithms and ROC analysis selected diagnostic feature genes, and drug-gene interactions were investigated.

Main Results:

  • 3460 DEGs related to PANoptosis were identified, enriched in cytokine signaling and apoptosis pathways.
  • Eight hub PANoptosis genes were identified, with significantly higher PANoptosis scores in AKI patients.
  • CASP8, CASP4, SFN, FAS, and CASP1 were selected as key diagnostic markers, with CASP8 showing high predictive value (AUC=0.850).
  • These genes correlated with immune cell infiltration and showed potential drug associations, validated in a rat model.

Conclusions:

  • PANoptosis-related genes serve as promising diagnostic biomarkers for AKI.
  • These genes represent potential therapeutic targets for AKI treatment.
  • The findings underscore the role of PANoptosis in AKI-associated immune dysregulation.
Keywords:
Acute kidney injuryapoptosisdiagnosisimmune microenvironmentnecroptosispyroptosis

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