Identification of biomarkers co-associated with M1 macrophages, ferroptosis and cuproptosis in alcoholic hepatitis by bioinformatics and experimental verification

BackgroundsAlcoholic hepatitis (AH) is a major health problem worldwide. There is increasing evidence that immune cells, iron metabolism and copper metabolism play important roles in the development of AH. We aimed to explore biomarkers that are co-associated with M1 macrophages, ferroptosis and cuproptosis in AH patients. MethodsGSE28619 and GSE103580 datasets were integrated, CIBERSORT algorithm was used to analyze the infiltration of 22 types of immune cells and GSVA algorithm was used to calculate ferroptosis and cuproptosis scores. Using the WGCNA R package, we established a gene co-expression network and analyzed the correlation between M1 macrophages, ferroptosis and cuproptosis scores and module characteristic genes. Subsequently, candidate genes were screened by WGCNA and differential expression gene analysis. The LASSO-SVM analysis was used to identify biomarkers co-associated with M1 macrophages, ferroptosis and cuproptosis. Finally, we validated these potential biomarkers using GEO datasets (GSE155907, GSE142530 and GSE97234) and a mouse model of AH. ResultsThe infiltration level of M1 macrophages was significantly increased in AH patients. Ferroptosis and cuproptosis scores were also increased in AH patients. In addition, M1 macrophages, ferroptosis and cuproptosis were positively correlated with each other. Combining bioinformatics analysis with a mouse model of AH, we found that ALDOA, COL3A1, LUM, THBS2 and TIMP1 may be potential biomarkers co-associated with M1 macrophages, ferroptosis and cuproptosis in AH patients. ConclusionWe identified 5 potential biomarkers that are promising new targets for the treatment and diagnosis of AH patients.

Automated summary

In this study, potential biomarkers co-associated with M1 macrophages, ferroptosis, and cuproptosis in alcoholic hepatitis (AH) patients were identified through gene expression analysis and immune cell infiltration level. ALDOA, COL3A1, LUM, THBS2, and TIMP1 were discovered as potential biomarkers through validation in a mouse model and additional datasets, suggesting their promise for the treatment and diagnosis of AH.