HAUS6 as a potential prognostic and immunological biomarker: validation from pan-cancer analysis to hepatocellular carcinoma

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BACKGROUND: The HAUS augmin like complex subunit 6 (HAUS6) is associated with cytokinesis.HAUS6 has only been reported in a few cancers. To date, there are no published studies about the potential biological features and clinical meaning of HAUS6 in pan-cancer. METHODS: We used TCGA, GTEx and UALCAN databases to explore HAUS6 expression and to analyze its associated prognosis in pan-cancer. Mutation, m6A and DNA methylation analyses were performed by databases of cBioPortal, MethSurv, UALCAN, and SRAMP. We identified genes interacting and associated with HAUS6 by GeneMania and GEPIA2, respectively. We used the ESTIMATE package, TISIDB, TIDE, and TIMSO to investigate the correlation between HAUS6 and immune infiltration and immunotherapy. We investigated the relationship of HAUS6 with tumor heterogeneity, stemness and drug sensitivity. In addition, we constructed a nomograph and performed differential analyses based on HAUS6 in HCC, and RT-qPCR and immunohistochemistry were performed to validate the expression in HCC and normal tissues. Finally, the proliferative, migratory and invasive capacities of HAUS6 in HCC were verified using CCK-8, colony formation, Transwell array and wound healing assays. RESULTS: After pan-cancer analysis, HAUS6 showed different expression levels in tumor tissues and normal tissues, and correlated with prognosis, indicating its potential as a diagnostic and prognostic biomarker. HAUS6 mutations were identified in 19 of 27 tumor types. Notably, HAUS6 expression was closely associated with m6A, DNA methylation, tumor heterogeneity, stemness, immune cell infiltration and immune checkpoints. Furthermore, HAUS6 showed significant predictive value for immunotherapy outcomes and was potentially associated with multiple drugs. In HCC, HAUS6 was identified as an independent risk factor; functional enrichment analyses highlighted that increased HAUS6 expression is related to the cell cycle and multiple cancer signaling pathways. Experimental validation shows that the mRNA (P = 0.028) and protein (P < 0.001) levels of HAUS6 in HCC tissues are highly consistent with the TCGA prediction trend. In vitro experiments further demonstrated that HAUS6 silencing inhibited HCC cell proliferation, migration and invasion. CONCLUSIONS: This study highlights the importance of HAUS6 in cancer biology. HAUS6 may be a biomarker for diagnosis and prediction of prognosis as well as a target for tumor immunotherapy.

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