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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 ( HK 2), which is involved in glycolysis, and phosphorylated pyruvate dehydrogenase‐E1α (p‐ PDH ), which is involved in oxidative phosphorylation (OxPhos). Immunohistochemical analyses using anti‐ HK 2 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  HK 2 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  CRC s than in left‐sided  CRC s ( P =  0.0883). In survival analysis, the combined evaluation of positive  HK 2 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  HK 2 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.

cancer science

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