Comprehensive analysis of Fraser syndrome 1 as a potential biomarker and therapeutic target in hepatocellular carcinoma

Fraser syndrome 1 ( FRAS1 ) is an extracellular matrix (ECM) protein that plays a vital role in epidermal basement membrane adhesion and organ development. FRAS1 also plays a crucial role in cancer development. However, its role in hepatocellular carcinoma (HCC) remains to be explored. The present work assessed the association between FRAS1 expression and HCC development. FRAS1 expression analysis was conducted by means of The Cancer Genome Atlas (TCGA)/Genotype-Tissue Expression Project (GTEx) databases and validated by the Gene Expression Omnibus database and in vivo and in vitro experiments. Protein expression was assessed using the Clinical Proteomic Tumour Analysis Consortium database. A series of bioinformatics approaches and experiments was conducted to investigate the underlying oncogenic role of FRAS1 in HCC. FRAS1 at both genetic and protein levels were markedly elevated in hepatocellular carcinoma (HCC) specimens compared to non-cancerous tissues. Enhanced FRAS1 expression exhibited a robust correlation with aggressive clinical and pathological features. Individuals with upregulated FRAS1 demonstrated heightened metastatic potential and unfavorable clinical outcomes. Furthermore, FRAS1 showed significant associations with multiple tumor-infiltrating immune cell populations, particularly CD8 + T lymphocytes and their subsets. FRAS1 exhibited pro-tumour properties by activating several oncogenic signalling pathways. FRAS1 protein expression was significantly elevated in HCC tissues compared to paired adjacent tissues, as confirmed by immunohistochemistry and Western blot analysis. Double-stain immunofluorescence staining revealed a close association between FRAS1 and immune cell infiltration. Tumors derived from FRAS1 siRNA-treated mice exhibited significantly smaller volumes compared to controls. FRAS1 may serve as a potential therapeutic target and a valuable prognostic biomarker for HCC.