HIF1A is a prognostic biomarker of breast cancer and correlates with immunocyte infiltration
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Abstract:
Objective: To investigate the expression of hypoxia inducible factor 1 subunit alpha (HIF1A) in breast cancer (BC) and its relationship with prognosis and tumor immune cell infiltration in BC based on various cancer bioinformatics databases. Methods: The expression of HIF1A gene in BC tissues and its correlation with the prognosis and clinicopathological characteristics of patients were analyzed using the Oncomine, the Human Protein Atlas and TCGA databases, which were then verified in human breast cancer tissue specimens (93 cases of breast cancer tissues and 14 cases of benign breast disease tissues surgically resected from January 2011 to December 2015 in Renmin Hospital of Wuhan University). Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted to analyze the differentially expressed genes between HIF1A-high and HIF1A- low expression groups. The differences in the abundance of immune cell infiltration in samples with high and low HIF1A expression were assessed by CIBERSORT. Results: As indicated by bioinformatics data, HIF1A was highly expressed in BC tissues and predicted a better prognosis (P<0.05). The expression of HIF1A was associated with estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) levels in BC (all P<0.05). The GO biological function analysis and KEGG pathway enrichment analysis suggested that HIF1A might be involved in tumor immunoregulation. CIBERSORT analysis suggested the correlation between HIF1A and tumor immune cell infiltration, and found that activated memory CD4 + T cells, M0 and M1 macrophages were positively correlated with HIF1A expression, while Treg cells, activated NK cells, and M2 macrophages were negatively correlated with HIF1A expression (all P<0.05). Conclusion: HIF1A is involved in regulating the immunological activity of the tumor microenvironment and is related to the disease-free survival (DFS) of breast cancer patients. It can be served as a biomarker for graded diagnosis, immunotherapy and prognosis judgment of BC.