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.

中文翻译：

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乳腺癌中肿瘤糖酵解与免疫/炎症功能之间关系的综合分析。

背景技术代谢重编程，免疫逃避和肿瘤促进炎症是癌症的三个标志，为理解癌症的生物学提供了新的观点。我们的目的是弄清乳腺癌中肿瘤糖酵解与免疫/炎症功能之间的关系，这对于深入了解乳腺癌的生物学，治疗和预后具有重要意义。方法根据癌症基因组图谱（TCGA）项目中基于H＆E染色的数字化图像和乳腺癌的临床信息，使用mRNA转录组数据，肿瘤浸润淋巴细胞（TIL）图，探讨糖酵解相关基因的表达及其对预后的影响，以及不同免疫/炎症细胞在肿瘤微环境中的富集得分和双重作用。通过差异基因表达分析，基因本体论（GO）分析，京都基因与基因组百科全书（KEGG）分析，基因组富集分析（GSEA）和相关分析，研究了糖酵解活性与免疫/炎症功能之间的关系。结果与正常组织相比，大多数糖酵解相关基因在乳腺癌中的表达更高。磷酸甘油酸激酶1（PGK1）的较高表达与不良预后有关。高糖酵解组上调了免疫/炎症相关基因的表达，上调了免疫/炎症通路，特别是IL-17信号通路，同时增加了多种免疫/炎症细胞如Th2细胞和巨噬细胞的富集。然而，高糖酵解组与杀灭肿瘤的免疫细胞（如NKT细胞）浸润较少，免疫检查点表达较高（如PD-L1，CTLA4，FOXP3和IDO1）相关。结论总之，乳腺癌糖酵解活性的增强与促肿瘤免疫有关。肿瘤糖酵解与免疫/炎症功能之间的相互作用可以通过IL-17信号传导途径介导。