Comprehensive analysis of the association between tumor glycolysis and immune/inflammation function in breast cancer
Comprehensive analysis of the association between tumor glycolysis and immune/inflammation function in breast cancer
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DOI：
10.1186/s12967-020-02267-2
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发表时间：
2020-02-18
影响因子：
7.4
通讯作者：
Yi, Pengfei
中科院分区：
文献类型：
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作者：
Li, Wenhui;Xu, Ming;Yi, Pengfei
代谢重编程、免疫逃避和促肿瘤炎症是癌症的三个特征，为理解癌症生物学提供了新的视角。我们旨在了解乳腺癌背景下肿瘤糖酵解与免疫/炎症功能的关系，这对深入了解乳腺癌的生物学、治疗和预后具有重要意义。方法利用mRNA转录组数据、基于数字化h&e染色图像的肿瘤浸润淋巴细胞（TILs）图谱和来自癌症基因组图谱项目（TCGA）的乳腺癌临床信息，探讨糖酵解相关基因的表达和预后意义，以及不同免疫/炎症细胞在肿瘤微环境中的富集评分和双重作用。通过差异基因表达分析、基因本体（GO）分析、京都基因与基因组百科全书（KEGG）分析、基因集富集分析（GSEA）和相关分析，研究糖酵解活性与免疫/炎症功能的关系。结果大多数糖酵解相关基因在乳腺癌组织中的表达高于正常组织。高磷酸甘油酸激酶1 （PGK1）表达与不良预后相关。高糖酵解组免疫/炎症相关基因表达上调，免疫/炎症通路尤其是IL-17信号通路上调，Th2细胞、巨噬细胞等多种免疫/炎症细胞富集程度较高。而高糖酵解组肿瘤杀伤免疫细胞如NKT细胞浸润较低，免疫检查点如PD-L1、CTLA4、FOXP3和IDO1表达较高。结论乳腺癌糖酵解活性增强与肿瘤前免疫有关。肿瘤糖酵解与免疫/炎症功能的相互作用可能通过IL-17信号通路介导。
Background Metabolic reprogramming, immune evasion and tumor-promoting inflammation are three hallmarks of cancer that provide new perspectives for understanding the biology of cancer. We aimed to figure out the relationship of tumor glycolysis and immune/inflammation function in the context of breast cancer, which is significant for deeper understanding of the biology, treatment and prognosis of breast cancer. Methods Using mRNA transcriptome data, tumor-infiltrating lymphocytes (TILs) maps based on digitized H&E-stained images and clinical information of breast cancer from The Cancer Genome Atlas projects (TCGA), we explored the expression and prognostic implications of glycolysis-related genes, as well as the enrichment scores and dual role of different immune/inflammation cells in the tumor microenvironment. The relationship between glycolysis activity and immune/inflammation function was studied by using the differential genes expression analysis, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, gene set enrichment analyses (GSEA) and correlation analysis. Results Most glycolysis-related genes had higher expression in breast cancer compared to normal tissue. Higher phosphoglycerate kinase 1 (PGK1) expression was associated with poor prognosis. High glycolysis group had upregulated immune/inflammation-related genes expression, upregulated immune/inflammation pathways especially IL-17 signaling pathway, higher enrichment of multiple immune/inflammation cells such as Th2 cells and macrophages. However, high glycolysis group was associated with lower infiltration of tumor-killing immune cells such as NKT cells and higher immune checkpoints expression such as PD-L1, CTLA4, FOXP3 and IDO1. Conclusions In conclusion, the enhanced glycolysis activity of breast cancer was associated with pro-tumor immunity. The interaction between tumor glycolysis and immune/inflammation function may be mediated through IL-17 signaling pathway.