Identification of Basement Membrane Genes and Related Molecular Subtypes in Nonalcoholic Fatty Liver Disease

Basement membranes (BMs) are widely distributed and highly specialized extracellular matrix (ECM). The goal of this study was to explore novel genes associated with nonalcoholic fatty liver disease (NAFLD) from the perspective of BMs. Sequencing results of 304 liver biopsy samples about NAFLD were systematically obtained from the Gene Expression Omnibus (GEO) database. Biological changes during NAFLD progression and hub BM-associated genes were investigated by differential gene analysis and weighted gene co-expression network analysis (WGCNA), respectively. The nonalcoholic steatohepatitis (NASH) subgroups were identified based on hub BM-associated genes expression, as well as the differences in Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways and immune microenvironment between different subgroups were compared. Extracellular matrix (ECM) seems to play an important role in the development of NAFLD. Three representative BM-associated genes (ADAMTS2, COL5A1, and LAMC3) were finally identified. Subgroup analysis results suggested that there were significant changes in KEGG signaling pathways related to metabolism, extracellular matrix, cell proliferation, differentiation, and death. There were also changes in macrophage polarization, neutrophils, and dendritic cells abundance, and so on. In conclusion, the present study identified novel potential BM-associated biomarkers and further explored the heterogeneity of NASH that might provide new insights into the diagnosis, assessment, management, and personalized treatment of NAFLD.