Potential Role of Tumor Cell Metabolic Subtype in the Clinical Course of Hepatocellular Carcinoma

Abstract

INTRODUCTION: Tumor metabolism is critical in tumorigenesis and development. This study aims to evaluate the potential role and the prognostic value of tumor cell metabolism in the progression of hepatocellular carcinoma (HCC). METHODS: Systematic analyses were performed using genome, transcriptome, and clinical characteristics to evaluate the metabolic system in 673 HCC patients. We analyzed the impact of metabolism on the clinical course of HCC. Univariate and multivariate Cox proportional-hazards regression methods were used to screen overall survival (OS). RESULTS: Included HCC patients were categorized into cholesterogenic (25.3%), glycolytic (14.6%), mixed (10.4%), and quiescent (49.8%) types based on the glycolysis and cholesterol biosynthesis gene expression. The distribution of α-fetoprotein (AFP; <300 μg/L or ≥300 μg/L) but not TMN stages among the 4 metabolic subtypes showed significant differences (p < 0.05). The quiescent subtype was associated with a low AFP expression level (p < 0.05) and the glycolytic subtype was associated with a higher AFP level (p < 0.01). The mixed type and glycolytic type had a shorter median OS (p < 0.0001). And the metabolic subtype emerged as an independent predictor of HCC patients’ survival in multivariate analyses. CONCLUSION: These results suggest that the metabolic subtypes were consistent with AFP expression and may play a prognostic role in HCC patients. And the glycolytic metabolism-related genes may induce tumor progression in HCC.