FBXW8 is upregulated in hepatocellular carcinoma and promotes HCC cell malignancy

AIM: Investigate FBXW8 expression levels in hepatocellular carcinoma (HCC), its biological roles and prognostic significance. METHODS: Based on the analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases, the expression level of FBXW8 was investigated. The results were verified in clinical samples using quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Functional experiments (Cell Counting Kit-8, wound healing, and Transwell) were conducted on Huh7 and MHCC-97 H cells. Immune infiltration and methylation status were also evaluated. RESULTS: FBXW8 was significantly overexpressed in HCC tissues across multiple cohorts (TCGA, GSE25097, GSE54236; all p < 0.001), with consistent validation by qPCR and IHC in clinical specimens. Elevated FBXW8 expression correlated with aggressive clinicopathological characteristics, specifically, advanced tumor-node-metastasis staging, poor histological grade, and higher alpha-fetoprotein levels (all p < 0.05). High FBXW8 expression was associated with worse overall survival (hazard ratio [HR] = 1.52, p = 0.024), with Progression-free interval (HR = 1.45, p = 0.013) also adversely affected. Receiver operating characteristic analysis demonstrated that FBXW8 had diagnostic value. The areas under the curve in the TCGA, GSE25097 and GSE54236 datasets were 0.875, 0.837 and 0.716, respectively. The in vitro functional experiments demonstrated that FBXW8 overexpression promoted cell proliferation, migration, and invasion (all p < 0.05). The FBXW8 expression was positively correlated with T helper cells (r = 0.342), while it was negatively correlated with dendritic cells (r = - 0.379). Promoter hypermethylation of FBXW8 was observed in HCC, with three CpG sites associated with prognosis. CONCLUSION: FBXW8 functions as a prognostic biomarker and promotes HCC progression, indicating its therapeutic potential.