Uncovering potentially targetable genes in liver fibrosis via bioinformatics and experimental validation

Liver fibrosis is a major complication of chronic liver disease, and its treatment remains challenging due to the lack of effective anti-fibrotic therapies. Identifying potentially targetable genes may provide new therapeutic opportunities. This study integrated two liver fibrosis-related datasets (GSE14323 and GSE84044) and performed batch correction. Differentially expressed genes were screened using limma, modules associated with liver fibrosis were identified using WGCNA, and then intersection with a list of potential druggable genes was performed. Candidate genes were validated using ROC and immune infiltration analysis, and some candidate genes were validated in clinical liver samples using IHC and IF. In liver fibrosis tissues, eight genes (AQP1, CCL19, CXCL6, CXCL9, CXCL10, EPCAM, IGJ, and LUM) were upregulated and showed good diagnostic performance. These genes were enriched in pathways related to immune regulation, extracellular matrix remodeling, and inflammatory signaling. IHC and IF showed that AQP1 expression was upregulated. This study identified key target genes with diagnostic relevance in transcriptomic datasets, providing candidates for further validation and mechanistic studies.