Combined evaluation of hexokinase 2 and phosphorylated pyruvate dehydrogenase‐E1α in invasive front lesions of colorectal tumors predicts cancer metabolism and patient prognosis

Although numerous studies have shown the significance of cancer‐specific aerobic glycolysis, how glycolysis contributes to tumor invasion, a critical phenomenon in metastasis, remains unclear. With regard to colorectal cancer (CRC), we studied two critical gate enzymes, hexokinase 2 (HK2), which is involved in glycolysis, and phosphorylated pyruvate dehydrogenase‐E1α (p‐PDH), which is involved in oxidative phosphorylation (OxPhos). Immunohistochemical analyses using anti‐HK2 and p‐PDH antibodies were performed on surgically resected CRC samples (n = 104), and the expression in invasive front lesions of tumors was assessed. Positive HK2 expression correlated with extensive tumor diameter (P = 0.0460), advanced tumor depth (P = 0.0395), and presence of lymph node metastasis (P = 0.0409). Expression of p‐PDH tended to be higher in right‐sided CRCs than in left‐sided CRCs (P = 0.0883). In survival analysis, the combined evaluation of positive HK2 and negative p‐PDH was associated with reduced recurrence‐free survival (RFS) (P = 0.0169 in all stages and P = 0.0238 in Stage II and III patients, respectively). This evaluation could predict RFS more precisely than the independent evaluation. The present study indicated that high HK2 expression combined with low p‐PDH expression in the invasive front lesions of CRC tumors is predictive of tumor aggressiveness and survival of CRC cases. The correlation between aerobic glycolysis and colorectal cancer invasion remains unclear. In our study, combined evaluation of hexokinase 2 and phosphorylated pyruvate dehydrogenase‐E1α in invasive front lesions of colorectal tumors could predict cancer metabolism and patient prognosis.