Association between glycolysis markers and prognosis of liver cancer: a systematic review and meta-analysis

Abstract

Background In recent years, the capacity of tumor cells to maintain high levels of glycolysis, even in the presence of oxygen, has emerged as one of the main metabolic traits and garnered considerable attention. The purpose of this meta-analysis is to investigate the prognostic value of glycolysis markers in liver cancer. Methods PubMed, Embase, and Cochrane Library databases were searched for articles on glycolytic marker expression levels associated with the prognosis of liver cancer until April 2023. Stata SE14.0 was used to calculate the aggregate hazard ratios and 95% confidence intervals. Results Thirty-five studies were included. The worse overall survival (OS) (P < 0.001), disease-free survival (DFS) (P = 0.001), recurrence-free survival (RFS) (P = 0.004), and time to recurrence (TTR) (P < 0.001) were significantly associated with elevated expression of glycolysis markers. Higher expression of PKM2 (P < 0.001), STMN1 (P = 0.002), MCT4 (P < 0.001), GLUT1 (P = 0.025), HK-2 (P < 0.001), and CA9 (P < 0.001) were significantly related to shorter OS. Increased levels of PKM2 (P < 0.001), CA9 (P = 0.005), and MCT4 (P < 0.001) were associated with worse DFS. Elevated PKM2 expression (P = 0.002) was also associated with poorer RFS in hepatocellular carcinoma patients. GLUT2 expression was not correlated with the prognosis of liver cancer (P = 0.134). Conclusions Elevated expression of glycolysis markers was associated with worse OS, DFS, RFS, and TTR in patients with liver cancer. Therefore, these glycolysis markers could serve as potential prognostic markers and therapeutic targets in liver cancer. Trial registration PROSPERO registration: CRD42023469645.