Cuproptosis-Related Genes in Immune Infiltration and Diagnosis in Hepatitis B Virus-Related Acute Liver Failure

Abstract

Hepatitis B virus (HBV) infection poses a significant challenge to global health, particularly in developing countries such as China, where HBV-related acute liver failure (HBV-ALF) is a prominent cause of acute liver failure. This study investigated the effect of cuproptosis, a recently identified form of cell death, on immune infiltration in HBV-ALF. We mined the gene expression data of HBV-ALF from the Gene Expression Omnibus database. Through enrichment analysis of differentially expressed genes (DEGs), pathways related to the response to metal/copper ions and the acute inflammatory response were found to be enriched. We subsequently found that HBV-ALF tissues contained more copper ions and conducted an intersection analysis of DEGs and cuproptosis-related genes (CRGs), which resulted in the identification of 7 core cuproptosis-related DEGs (CR-DEGs) for further investigation with a diagnostic model. Immune infiltration analysis and unsupervised clustering analysis revealed distinct patterns in HBV-ALF and the possibility of crosstalk between ferroptosis and cuproptosis. Furthermore, we identified 17 transcription factors, 90 miRNAs, and 15 drugs that might interact with the 7 CR-DEGs. To validate our findings and their clinical significance, we verified the diagnostic value and immune infiltration patterns of the 7 CR-DEGs in both the testing dataset, cell line, and clinical samples. In conclusion, our findings indicated that these 7 CR-DEGs demonstrate promising diagnostic value and may represent viable therapeutic targets for individuals with HBV-ALF.

Keywords

acute liver failure / bioinformatics / cuproptosis / ferroptosis / hepatitis B virus / immune infiltration

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