目的： 借助多种癌症生物信息数据库研究乳腺癌组织中缺氧诱导因子1亚基α （HIF1A）的表达水平及其与乳腺癌患者预后及肿瘤免疫细胞浸润的关系。 方法： 利用Oncomine、人类蛋白质图谱、基因表达谱交互式分析（GEPIA）及TCGA数据库分析HIF1A基因在乳腺癌组织中的表达及其与患者预后、临床病理特征的关系，并在中国人乳腺癌组织标本（选用2011年1月至2015年12月中国武汉大学人民医院手术切除的93例乳腺癌组织和14例良性乳腺疾病组织）中进行验证。对HIF1A高低表达组间的差异基因进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析，用Cibersort R软件评估HIF1A高低表达样本中免疫细胞浸润丰度差异。 结果： 生物信息数据显示，HIF1A在乳腺癌组织中高表达，预示着患者DFS预后更好（P<0.05）。HIF1A的表达与雌激素受体（ERP）、孕激素受体（PR）和人表皮生长因子受体2 （HER2）表达相关（均P<0.05）。GO生物功能及KEGG通路富集分析结果提示，HIF1A可能参与肿瘤免疫调节等生物活动。使用Cibersort分析结果显示，HIF1A与肿瘤免疫细胞浸润之间具有相关性（均P<0.01），发现活化记忆CD4 + T细胞、M0和M1型巨噬细胞与HIF1A表达呈正相关，在乳腺癌组织中高表达，Treg细胞、活化NK细胞、M2型巨噬细胞与HIF1A表达呈负相关（均P<0.01）。 结论： HIF1A参与调节肿瘤微环境的免疫活性，与乳腺癌患者DFS相关，其可能成为乳腺癌分级诊断、免疫治疗和预后判断的生物标志物。

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.

R737.9; R730.2; R730.7

国家自然科学青年基金资助项目（No.81302314）；湖北省自然科学基金资助项目（No.2020CFA026）