The relationship between the metabolic enzyme hexokinase 2 and cancer immunity: a pan-cancer analysis

Abstract

Abstract Background: Hexokinase 2 (HK2) takes on critical significance in glycolysis as the primary rate-limiting enzyme, which can carefully control the phosphorylation of glucose. The non-metabolic functions exhibited by HK2 have been extensively reported as immunometabolism research has been leaping forward. Nevertheless, the non-canonical functions exhibited by HK2 on cancer immunity have been rarely investigated. Methods: HK2 expression was investigated in nine cancer types with the datasets originating from The Cancer Genome Atlas (TCGA). Subsequently, survival analysis (e.g., progression free interval (PFI), disease-specific survival (DSS) and overall survival (OS)) was performed in different tumor diseases. Moreover, we determined the relationship coefficient of clinicopathologic features and HK2 expression. Besides, the relationship coefficient of clinicopathologic features and HK2 expression was calculated. Lastly, the relationships of microsatellite instability (MSI), tumor mutation burden (TMB), prognosis, and HK2 expression were determined. Results: HK2 demonstrated profound and pervasive overexpression across most tumour diseases. Conclusions: This study revealed that HK2 may contribute to shaping the immunosuppressive tumor microenvironment (TME) and facilitate the progression of tumor in LGG and GBM by affecting the anti-tumor functions of immune cells.