Exploring the Prognostic Value, Immune Implication and Biological Function of H2AFY Gene in Hepatocellular Carcinoma

BackgroundHepatocellular carcinoma (HCC) is an extremely malignant cancer with poor survival. H2AFY gene encodes for a variant of H2A histone, and it has been found to be dysregulated in various tumors. However, the clinical value, biological functions and correlations with immune infiltration of H2AFY in HCC remain unclear. MethodsWe analyzed the expression and clinical significance of H2AFY in HCC using multiple databases, including Oncomine, HCCDB, TCGA, ICGC, and so on. The genetic alterations of H2AFY were analyzed by cBioPortal and COSMIC databases. Co-expression networks of H2AFY and its regulators were investigated by LinkedOmics. The correlations between H2AFY and tumor immune infiltration were explored using TIMER, TISIDB databases, and CIBERSORT method. Finally, H2AFY was knocked down with shRNA lentiviruses in HCC cell lines for functional assays in vitro. ResultsH2AFY expression was upregulated in the HCC tissues and cells. Kaplan-Meier and Cox regression analyses revealed that high H2AFY expression was an independent prognostic factor for poor survival in HCC patients. Functional network analysis indicated that H2AFY and its co-expressed genes regulates cell cycle, mitosis, spliceosome and chromatin assembly through pathways involving many cancer-related kinases and E2F family. Furthermore, we observed significant correlations between H2AFY expression and immune infiltration in HCC. H2AFY knockdown suppressed the cell proliferation and migration, promoted cycle arrest, and apoptosis of HCC cells in vitro. ConclusionOur study revealed that H2AFY is a potential biomarker for unfavorable prognosis and correlates with immune infiltration in HCC.

Automated summary

This study revealed that H2AFY is upregulated in HCC tissues and cells, and high H2AFY expression is an independent prognostic factor for poor survival in HCC patients. Functional network analysis showed that H2AFY and its co-expressed genes regulate cell cycle, mitosis, spliceosome, and chromatin assembly through pathways involving various cancer-related kinases and E2F family. Moreover, significant correlations were observed between H2AFY expression and immune infiltration in HCC. Knockdown of H2AFY suppressed cell proliferation and migration, promoted cell cycle arrest, and induced apoptosis in HCC cells in vitro.