Open AccessCombined evaluation of hexokinase 2 and phosphorylated pyruvate dehydrogenase‐E1α in invasive front lesions of colorectal tumors predicts cancer metabolism and patient prognosis
Author(s) -
Hamabe Atsushi,
Yamamoto Hirofumi,
Konno Masamitsu,
Uemura Mamoru,
Nishimura Junichi,
Hata Taishi,
Takemasa Ichiro,
Mizushima Tsunekazu,
Nishida Naohiro,
Kawamoto Koichi,
Koseki Jun,
Doki Yuichiro,
Mori Masaki,
Ishii Hideshi
Publication year - 2014
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12487
Subject(s) - glycolysis , colorectal cancer , hexokinase , metastasis , medicine , cancer , immunohistochemistry , pyruvate dehydrogenase complex , oxidative phosphorylation , cancer research , oncology , pyruvate kinase , anaerobic glycolysis , biology , enzyme , metabolism , biochemistry
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.