Multiomics reveals the role of macrophage-vascular endothelial cell interactions in the hepatoblastoma tumor microenvironment

Abstract

Abstract Background Hepatoblastoma is a common tumor in childhood, characterized by immature histology and diverse cell lineages. The purpose of this study is to identify the genes that are abnormally expressed in hepatoblastoma, and to explore and verify the targets of intercellular communication that affect the tumor immune microenvironment. Methods Through comprehensive analysis of gene expression from GSE133039 and GSE180664 data sets, the differentially expressed genes in cancer tissues and adjacent tissues were obtained. GO and KEGG enrichment analysis is used to predict the biological function and signal transduction pathway of differential expression gene enrichment. Use cytoscape to build PPI network to filter hubgene; Construct correlation analysis of immune cell infiltration to infer the correlation between immune cells. Combined with single-cell transcriptome data, further reveal the relationship between cells and signal targets of cell communication. Results 58 differentially expressed genes with high expression and 94 differentially expressed genes with low expression were obtained from the two data sets of hepatoblastoma. They were mainly involved in the signal transduction related to metastasis. PPI network screened 50 hubgenes. The correlation analysis of immune cell infiltration of different genes showed that macrophages were significantly correlated with endothelial cells. Combined with the analysis of single-cell transcriptome data, hepatoblastoma was divided into 11 cell subpopulations, and 16 genes in hubgene were expressed in different cell subpopulations, in which LFNG was highly expressed in macrophages and monocytes, which served as the target of intercellular communication to promote the development of hepatoblastoma. Conclusion In this study, we identified the genes that were abnormally expressed in hepatoblastoma, and affected the cellular communication of hepatoblastoma through LFNG target, thus affecting the progress of tumor. Therefore, LFNG may become a therapeutic target for hepatoblastoma.