Abstract
Background: Hepatitis B virus (HBV)-associated liver cirrhosis, characterized by progressive fibrosis and regenerative nodule formation, remains a critical public health concern due to its high risk of progression to hepatocellular carcinoma (HCC). The matrisome-comprising extracellular matrix (ECM) components such as collagens, laminins, fibronectin, glycoproteins, and proteoglycans-plays a pivotal role in disease pathogenesis. Previous studies have shown that HBV infection modulates ECM composition and activates fibrogenic responses through hepatic stellate cells, contributing to cirrhosis and eventual HCC development. However, key ECM-related genes driving HBV-induced cirrhosis remain poorly understood. Methods: Bulk RNA-seq data from 30 normal and 30 HBV-related cirrhotic liver tissues were analyzed. Differentially expressed genes (DEGs) were identified using the Limma package based on thresholds of p < 0.01 and |log2 fold change| > 1. ECM-related genes were curated from the Molecular Signatures Database (MsigDB). Functional significance was assessed via random forest classification (accuracy: 91%, recall: 90%), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Results: Among 14,470 analyzed genes, 2125 were upregulated and 3689 downregulated in cirrhotic tissues. Upregulated genes (COX6B1, RPS10) were linked to metabolic reprogramming, while downregulated genes (PLCG2, ARHGEF12) implicated immune dysregulation. A subset of 274 ECM-related DEGs (178 upregulated, 96 downregulated) was identified, including CTSA, CRELD2, MAPK10, and ITGA1. Pathway analysis highlighted dysregulation of Ras/MAPK and ERBB signaling pathways associated with fibrogenesis and tumorigenesis. Conclusions: This bioinformatics study delineates key matrisome-associated genes and pathways in HBV-related cirrhosis, offering novel insights into potential biomarkers and therapeutic targets. Further validation in larger cohorts is warranted to confirm clinical relevance.