FAT4 Overexpression in Peripheral Blood Mononuclear Cells and Tumor Tissues is Associated With a Favorable Prognosis and Promotes Immune Cell Infiltration in Hepatocellular Carcinoma

Abstract Purpose: To identify prognostically relevant genes in hepatocellular carcinoma, and to investigate whether gene expression in peripheral blood mononuclear cells (PBMCs) and hepatocellular carcinoma tissues can be used as a diagnostic and prognostic marker. Methods: Using RNA-sequencing, gene expression was examined in PBMCs from patients with advanced hepatocellular carcinoma who survived or died. The expression of the top 10 genes in the survival group was validated.Results: The Gene Expression Omnibus and The Cancer Genome Atlas databases were used to analyze FAT atypical cadherin 4 (FAT4) transcript levels in PBMCs and in hepatocellular carcinoma and normal tissues. FAT4 expression was lower in hepatocellular carcinoma than in normal PBMCs and tissues. Kaplan–Meier analysis suggested that downregulated FAT4 was associated with a relatively poor prognosis. The correlation between FAT4 expression and immune cell infiltration was also explored using Tumor Immune Estimation Resource, Gene Expression Profiling Interactive Analysis 2, and the Tumor and Immune System Interaction Database. FAT4 overexpression was positively correlated with immune cell infiltration, several immune cell markers, and immune checkpoint expression. MicroRNAs regulating FAT4 expression were identified using correlation, expression, and survival analyses. Hsa-miR-93-5p was the most likely upstream microRNA of FAT4 in hepatocellular carcinoma.Conclusion: FAT4 is highly expressed in PBMCs and hepatocellular carcinoma tissues, indicating a favorable prognosis and immune cell infiltration in hepatocellular carcinoma, and revealing the potential role of miRNA-93-5p-mediated downregulation of FAT4 in hepatocellular carcinoma immunology. Our findings provide a new direction for the development of novel immunotherapy targets for hepatocellular carcinoma.