AUTHOR=Huang Yongbiao , Huang Shanshan , Ma Li , Wang Yali , Wang Xi , Xiao Lingyan , Qin Wan , Li Long , Yuan Xianglin 

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

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.723293

DOI=10.3389/fimmu.2021.723293

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>Hepatocellular carcinoma (HCC) is an extremely malignant cancer with poor survival. <italic>H2AFY</italic> 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 <italic>H2AFY</italic> in HCC remain unclear.</p></sec><sec><title>Methods</title><p>We analyzed the expression and clinical significance of <italic>H2AFY</italic> in HCC using multiple databases, including Oncomine, HCCDB, TCGA, ICGC, and so on. The genetic alterations of <italic>H2AFY</italic> were analyzed by cBioPortal and COSMIC databases. Co-expression networks of <italic>H2AFY</italic> and its regulators were investigated by LinkedOmics. The correlations between <italic>H2AFY</italic> and tumor immune infiltration were explored using TIMER, TISIDB databases, and CIBERSORT method. Finally, <italic>H2AFY</italic> was knocked down with shRNA lentiviruses in HCC cell lines for functional assays <italic>in vitro</italic>.</p></sec><sec><title>Results</title><p><italic>H2AFY</italic> expression was upregulated in the HCC tissues and cells. Kaplan–Meier and Cox regression analyses revealed that high <italic>H2AFY</italic> expression was an independent prognostic factor for poor survival in HCC patients. Functional network analysis indicated that <italic>H2AFY</italic> 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 <italic>H2AFY</italic> expression and immune infiltration in HCC. <italic>H2AFY</italic> knockdown suppressed the cell proliferation and migration, promoted cycle arrest, and apoptosis of HCC cells <italic>in vitro</italic>.</p></sec><sec><title>Conclusion</title><p>Our study revealed that <italic>H2AFY</italic> is a potential biomarker for unfavorable prognosis and correlates with immune infiltration in HCC.</p></sec>