Cuproptosis-Related Genes in Immune Infiltration and Diagnosis in Hepatitis B Virus-Related Acute Liver Failure
Jingwen Deng1, Tao Zhu2, Yueyang Wang3,4
1Department of Medical Oncology Sir Run Run Shaw Hospital School of Medicine Zhejiang University Hangzhou China.
Insights
This study reveals that cuproptosis, a cell death process involving copper, is linked to immune changes in Hepatitis B virus-related acute liver failure (HBV-ALF). Seven core genes show diagnostic potential for HBV-ALF.
Area of Science:
- Hepatology
- Immunology
- Cell Death Research
Background:
- Hepatitis B virus (HBV) infection is a global health concern, with HBV-related acute liver failure (HBV-ALF) being a major cause of liver failure in China.
- Cuproptosis, a novel form of programmed cell death regulated by copper, has emerged as a significant factor in cellular processes.
Purpose of the Study:
- To investigate the role of cuproptosis in immune infiltration within HBV-related acute liver failure (HBV-ALF).
- To identify potential diagnostic biomarkers and therapeutic targets for HBV-ALF based on cuproptosis-related genes.
Main Methods:
- Utilized gene expression data from the Gene Expression Omnibus (GEO) database for HBV-ALF.
- Performed enrichment analysis of differentially expressed genes (DEGs) and intersection analysis with cuproptosis-related genes (CRGs).
- Conducted immune infiltration analysis, unsupervised clustering, and validation in clinical samples.
Main Results:
- Enrichment analysis highlighted pathways related to copper ion response and acute inflammation in HBV-ALF.
- Identified 7 core cuproptosis-related DEGs (CR-DEGs) with diagnostic value for HBV-ALF.
- Revealed distinct immune infiltration patterns and potential crosstalk between ferroptosis and cuproptosis in HBV-ALF.
Conclusions:
- The 7 identified CR-DEGs show significant diagnostic potential for HBV-ALF.
- These CR-DEGs may serve as novel therapeutic targets for managing HBV-ALF.
- Cuproptosis plays a crucial role in the immune landscape of HBV-ALF, offering new avenues for treatment.
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.
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