Comprehensive Analysis of the Relationship Between Metabolic Reprogramming and Immune Function in Prostate Cancer

Abstract

Weijie Xie,1 Huan Guo,1 Jiawei Zhang,1 Li Hu,2 Yuqi Wu,1 Xiangwei Wang1,3 1Department of Urology & Carson International Cancer Center, Shenzhen University General Hospital & Shenzhen University Clinical Medical Academy Center, Shenzhen University, Shenzhen, People’s Republic of China; 2Department of Physiology, Shantou University of Medical College, Shantou, People’s Republic of China; 3Department of Urology, 3rd Affiliated Hospital and Department of Perioperative Medicine of Southern University of Science and Technology, Southern University of Science and Technology, Shenzhen, People’s Republic of ChinaCorrespondence: Xiangwei Wang; Yuqi WuDepartment of Urology & Carson International Cancer Center, Shenzhen University General Hospital & Shenzhen University Clinical Medical Academy Center, Shenzhen University, No. 1098, Xueyuan Road, Shenzhen University City, Nanshan District, Shenzhen, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]; [email protected]: Prostate cancer is the most common malignant urinary tumor among men. Treatments are currently unsatisfactory for advanced prostate cancer. Cancer biology remains the basis for developing new antitumor drugs. Therefore, it is crucial to study the metabolic reprogramming, immune microenvironment, and immune evasion of tumors. This study aimed to clarify the relationship between tumor glycolysis and immune function in prostate cancer.Materials and Methods: We downloaded the gene expression matrix and clinical data of prostate cancer from The Cancer Genome Atlas. We studied the expression profiles and prognostic significance of glycolysis-related genes and used CIBERSORT to identify the proportion of tumor-infiltrating immune cells. Through differential gene expression analysis, gene ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, gene set enrichment analysis, and correlation analysis, we further explored the relationship between glycolytic activity and immune function. We also performed immunohistochemistry, Western blot and RT-qPCR experiments using human prostate cancer tissue and cell lines to verify the expression of some glycolytic genes, macrophage infiltration and polarization.Results: Among glycolysis-related genes, the expression of SLC16A3 in prostate cancer tissues was lower than that in normal tissues, but its high expression was associated with poor prognosis. In the high SLC16A3 expression group, several glycolysis-related genes also showed high expression, which was confirmed by immunohistochemistry experiments and Western blot. In high-glycolysis group, the expression of immune-related genes and the interleukin-17 (IL-17) signaling pathway were upregulated. CD8+ T cells, regulatory T cells, macrophages, and other immune cells were highly enriched. Among them, M2 macrophage infiltration was associated with poor prognosis.Conclusion: The enhanced glycolytic activity of prostate cancer may contribute to the formation of a pro-tumor immune microenvironment. The IL-17 signaling pathway may play an important mediating role in the interaction between tumor glycolysis and immune function.Keywords: glycolysis, tumor-infiltrating immune cells, IL-17 signaling pathway, TCGA

Keywords

• glycolysis
• tumor-infiltrating immune cells
• il-17 signaling pathway
• tcga