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

Atsushi Hamabe, Hirofumi Yamamoto, Masamitsu Konno, Mamoru Uemura, Junichi Nishimura, Taishi Hata, Ichiro Takemasa, Tsunekazu Mizushima, Naohiro Nishida, Koichi Kawamoto, Jun Koseki, Yuichiro Doki, Masaki Mori, Hideshi Ishii

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23 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1100-1108
Number of pages9
JournalCancer Science
Issue number9
Publication statusPublished - Sep 1 2014


All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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