Objective: The involvement of HBXIP in cancer development and cancer cell survival is well known. This work probed the potential of HBXIP as a prognostic biomarker in hepatic cell cancer (HCC).

Materials and methods: First, pan-cancer analysis of HBXIP expression was conducted using The Cancer Genome Atlas (TCGA) database to validate the expression of HBXIP in different cancers. The GSE14520 (GPL3721 Subset) database was used to validate HBXIP in HCC. The association between survival outcomes and prognostic factors was assessed employing univariate and multivariate survival analyses for TCGA Liver Hepatocellular Carcinoma. The biological function of the HBXIP Gene was annotated by gene set enrichment analysis. The relationship between HBXIP expression and immune cells and immune markers was analyzed from the Gene Expression Profiling Interactive Analysis (GEPIA) database.

Results: Malignant tissues demonstrated evident upregulation of HBXIP at transcriptional and protein levels over normal tissues (p < 0.05) with this elevated expression linked to an advanced tumor stage in HCC cohorts. Univariate analysis revealed an evident correlation emerged between prognosis and HBXIP for GSE14520 databases (p < 0.05). The disease-free survival (DFS) and overall survival (OS) (five-year values) were lower in samples demonstrating elevated HBXIP (HR: 2.413; 95% CI 1.601, 3.638; p < 0.001) and (HR: 1.613; 95% CI 1.446, 1.844; p = 0.003), respectively vs. lower HBXIP expression. HBXIP emerged as an independent factor in OS prognosis (HR 2.184; 95% CI 1.495, 3.196; p < 0.001) and DFS (HR 1.764; 95% CI 1.261, 2.466; p < 0.001), respectively according to multivariate analysis. Further, multiple Cox analyses in the validation cohort revealed that independent factors for OS were HBXIP, AJCC T stage, vascular invasion, and tumor status with the C-index score of 0.727 (95% CI, 0.704 to 0.750). HBXIP level showed a significantly positive association with tumor immune cell infiltration, and biomarkers of immune cells; besides, the rectum Rho GTPase effectors signaling pathway was also identified.

Conclusions: HCC advancement and survival involves HBXIP, which also emerged as a functional biomarker for HCC survival prediction.