Pan-Cancer analysis of clinical significance and associated molecular features of glycolysis

Background: Tumor glycolysis acts as a major promoter of carcinogenesis and cancer progression. Given its complex mechanisms and interactions, a comprehensive analysis to reveal its clinical significance and molecular features is urgent. Materials: and Methods Based on a well-established glycolysis gene expression signature, we quantified 8633 patients across different cancer types from The Cancer Genome Atlas (TCGA) and evaluated their prognostic associations. High tumor glycolytic activity correlated with inferior overall survival in pan-cancer patients (hazard ratio: 1.70, 95% confidence interval: 1.20–2.40, P = 0.003). The prognostic value of glycolysis was stable regardless of clinical parameters and correlated with molecular subtypes. The prognostic significance of glycolysis was validated using another three independent datasets. In addition, genome, transcriptome, and proteome profiles were utilized to characterize distinctive molecular features associated with glycolysis. Results: Mechanistically, glycolysis fulfilled the fundamental needs of tumor proliferation in multiple ways. Exploration of the relationships between glycolysis and tumor infiltrating immune cells showed that glycolysis enabled immune evasion of tumor cells. Mammalian target of rapamycin inhibitors and dopamine receptor antagonists represent classes of compounds that can effectively reverse the glycolytic status of cancers. Conclusion: Our study provides an in-depth molecular understanding of tumor glycolysis and may have practical implications for clinical cancer therapy.