Identification of lactate metabolism-related genes for glioma metabolic reprogramming

Abstract Purpose: Alternation in the metabolic mechanism of tumor cells and immune cell infiltration in the tumor area leads to the formation of glioma immunosuppressive microenvironment, which promotes tumor immune escape and limits the efficacy of glioma immunotherapy. Our study aimed to identify lactate-metabolism-related molecules involved in the reprogramming of glioma metabolic pathways and to explore whether they could be potential targets for glioma. Methods: Based on the screening criteria of |logFC|>1, adjusted p < 0.05, and multivariate Cox regression analysis, we identified differentially expressed lactate metabolism-related genes (LMGs) in gliomas and depicted receiver operating characteristic (ROC) curves and nomogram to evaluate its clinical predictive performance. Then, we studied the regulation of LMGs in the tumor microenvironment and their reliability as potential targets for glioma therapy. Results: LDHB, PKM, ICAM3, and PDK1 were closely associated with the prognosis of glioma patients. The involvement of these four LMGs in the reprogramming of glioma metabolism led to lactate accumulation in the tumor microenvironment, which reduced the sensitivity of patients in the high-risk group to immunotherapy. Conclusion: Remodeling the glioma immunosuppressive microenvironment via targeting LMGs may improve the responsiveness of T cell immunotherapy, which becomes a new and improved alternative for glioma treatment.