HIF-1α is an important target for future research on the etiology and treatment of biliary atresia

Abstract Purpose of the study: In this study, our objective was to discover and immunologically profile clusters of molecules associated with copper-induced cell death in biliary atresia (BA) by employing a bioinformatics approach. We conducted an analysis of the GSE46960 dataset, sourced from the Gene Expression Omnibus (GEO), to gain insights into the involvement of copper-related molecular clusters in the development of BA. Study design: We conducted our study using liver samples collected from 64 children diagnosed with biliary atresia and compared them with 14 age-matched children suffering from other cholestatic diseases. Our investigation revolved around the identification of molecular clusters based on cuproptosis-related genes, while also examining the associated immune cell infiltration. To pinpoint genes specific to each cluster, we employed the Weighted Gene Co-expression Network Analysis (WGCNA) algorithm. Results: We identified dysregulated cuproptosis-related genes and observed activated immune responses in the comparison between biliary atresia and non-biliary atresia control groups. Within biliary atresia, we categorized two distinct cuproptosis-related molecular clusters. Our analysis of immune infiltration indicated notable differences in immune profiles between these two clusters, with Cluster2 displaying relatively higher levels of immune infiltration. Functional analysis further revealed that the cluster-specific Differentially Expressed Genes (DEGs) in Cluster2 were closely associated with a variety of immune responses. Conclusions: Our study provides a comprehensive depiction of the intricate relationship between copper-induced cell death and biliary atresia. Previous research has suggested a potential link between the activation of the HIF-1alpha pathway and the development of biliary atresia, and the findings presented in this paper lend support to this hypothesis.