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

Exploring the Prognostic Value, Immune Implication and Biological Function of H2AFY Gene in Hepatocellular Carcinoma.
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探讨 H2AFY 基因在肝细胞癌中的预后价值、免疫意义和生物学功能。

DOI:
10.3389/fimmu.2021.723293
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发表时间:
2021
影响因子:
7.3
通讯作者:
Yuan X
Yuan X
中科院分区:
医学2区
文献类型:
--
作者:
Huang Y;Huang S;Ma L;Wang Y;Wang X;Xiao L;Qin W;Li L;Yuan X

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肝细胞癌(HCC)是一种恶性程度极高的癌症,生存率极低。H2 AFY基因编码H2 A组蛋白的一种变体,并且已发现其在多种肿瘤中失调。然而,H2 AFY的临床价值、生物学功能及其与肝癌免疫浸润的关系尚不清楚。利用Oncomine、HCCDB、TCGA、ICGC等数据库分析H2 AFY在HCC中的表达及临床意义,利用cBioPortal和COSMIC数据库分析H2 AFY的基因变异。通过LinkedOmics研究了H2 AFY及其调节剂的共表达网络。采用TIMER、TISIDB数据库和CIBERSORT方法分析H2 AFY与肿瘤免疫浸润的相关性。最后,在HCC细胞系中用shRNA慢病毒敲低H2 AFY用于体外功能测定。 H2 AFY在HCC组织和细胞中表达上调。Kaplan-Meier和考克斯回归分析显示H2 AFY高表达是HCC患者生存率低的独立预后因素。功能网络分析表明,H2 AFY及其共表达基因通过多种肿瘤相关激酶和E2 F家族参与调控细胞周期、有丝分裂、剪接体和染色质组装。此外,我们观察到H2 AFY表达与HCC中的免疫浸润之间的显著相关性。H2 AFY基因敲低可抑制肝癌细胞的增殖和迁移,促进细胞周期阻滞和凋亡。我们的研究表明,H2 AFY是一个潜在的生物标志物,预后不良,并与免疫浸润在肝癌。
Hepatocellular 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. We 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. H2AFY 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. Our study revealed that H2AFY is a potential biomarker for unfavorable prognosis and correlates with immune infiltration in HCC.
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