HAUS6 serves as a potential prognostic and immunotherapy biomarker in hepatocellular carcinoma

Abstract HAUS6, a subunit of the HAUS augmin-like complex, is involved in cytokinesis. It has been reported in several cancers, yet its role in hepatocellular carcinoma (HCC) progression remains unclear. Therefore, we performed a comprehensive bioinformatics analysis to investigate HAUS6’s role in HCC progression. HAUS6 mRNA and protein expression were analyzed using data from public databases and validated by immunohistochemistry and Western blotting. Logistic and Cox regression analyses, receiver operating characteristic curves, and Kaplan–Meier survival analysis were performed to assess the association between HAUS6 expression and HCC clinicopathological characteristics. Nomograms and calibration curves were constructed to predict overall survival in HCC patients. Functional enrichment analysis was conducted to identify potential pathways associated with HAUS6 in HCC progression. We further evaluated the correlations between HAUS6 expression and immune cell infiltration, immune checkpoint molecules, chemokines, and their receptors. The association between HAUS6 expression and the half-maximal inhibitory concentration (IC50) of anticancer chemotherapy drugs in HCC was also assessed. Finally, CCK-8, colony formation, Transwell migration/invasion, wound healing, and murine subcutaneous xenograft assays were used to evaluate the effects of HAUS6 on HCC cell proliferation, migration, and invasion. HAUS6 is upregulated in HCC tumor tissues and effectively distinguishes them from adjacent non-tumor liver tissues. HAUS6 expression levels are associated with HCC clinical stage, histopathological grade, and clinicopathological characteristics, and serve as an independent predictor of significantly associated with overall survival, disease specific survival, and progression free survival in HCC patients. Gene set enrichment analysis identified immune-related pathways among the differentially expressed genes linked to HAUS6. Furthermore, HAUS6 expression in HCC tissues shows significant correlations with immune cell infiltration, immune checkpoint molecules, chemokines, and their receptors. In vitro and in vivo functional assays demonstrated that HAUS6 knockdown significantly suppresses HCC cell proliferation, migration, and invasion. HAUS6 may serve as a promising biomarker for HCC diagnosis and prognosis and as a potential therapeutic target, holding certain implications for the development of HCC-targeted therapies.