Purpose
Hepatocellular carcinoma (HCC) is the third leading cause of cancer related death, and its molecular mechanisms have not been fully elucidated. The aim of this work is to discover the association between immune microenvironment changes and pyroptosis molecular mechanisms in HCC.
Methods
Select gene expression profiles from the comprehensive gene expression database, establish protein-protein interaction networks, and perform functional enrichment analysis using databases such as the Kyoto Encyclopedia of Genes and Genomes (KEGG). Single cell identification of HCC cell types and malignant cells, trajectory analysis and intercellular signal communication further analyze the molecular mechanisms between immune cells and liver cells. Bioinformatics combined with single-cell analysis to elucidate the immune pyroptosis molecular mechanism underlying the development of HCC.
Results
The key hub genes of immune pyroptosis were validated through immunohistochemistry and in vitro experiments. Molecular biology has identified six focal death hub genes in HCC. Enrichment analysis shows that intersecting genes are enriched in immune responses, chemokine mediated signaling pathways, and inflammatory responses. The cellular clustering of single cells revealed the infiltration of immune cells, especially the polarization of macrophages, which plays an important role. Immunohistochemistry suggests that hub genes such as HMGB1, CYCS, GSDMD, IL-1β, NLRP3, and IL18 are the link between macrophage polarization and pyroptosis during HCC development.
Conclusions
In summary, the main molecular mechanisms underlying the pathogenesis of HCC are related to immune cell infiltration, particularly macrophage infiltration polarization that promotes the secretion of inflammatory factors leading to hepatocyte pyroptosis. Our study may guide future research on the macrophage pyroptosis signaling pathway in HCC.