Comprehensive analysis of the association between tumor glycolysis and immune/inflammation function in breast cancer

• DOI: 10.1186/s12967-020-02267-2
• Publication Date: 2020-02-18T13:03:03Z
• Authors: Wenhui Li; Ming Xu; Yu Li; Ziwei Huang; Jun Zhou; Qiuyang Zhao; Kehao Le; Fang Dong; Cheng Wan; Pengfei Yi
• Keywords: Inflammation; 0301 basic medicine; 0303 health sciences; Research; R; TCGA; Prognosis; 3. Good health; PGK1; 03 medical and health sciences; Breast cancer; Lymphocytes, Tumor-Infiltrating; IL-17 signaling pathway; Neoplasms; Tumor Microenvironment; Medicine; Humans; Glycolysis; Immune/inflammation function

Abstract 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.