TY - JOUR
T1 - Combined evaluation of hexokinase 2 and phosphorylated pyruvate dehydrogenase-E1α in invasive front lesions of colorectal tumors predicts cancer metabolism and patient prognosis
AU - Hamabe, Atsushi
AU - Yamamoto, Hirofumi
AU - Konno, Masamitsu
AU - Uemura, Mamoru
AU - Nishimura, Junichi
AU - Hata, Taishi
AU - Takemasa, Ichiro
AU - Mizushima, Tsunekazu
AU - Nishida, Naohiro
AU - Kawamoto, Koichi
AU - Koseki, Jun
AU - Doki, Yuichiro
AU - Mori, Masaki
AU - Ishii, Hideshi
N1 - Publisher Copyright:
© 2014 The Authors.
Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2014/9/1
Y1 - 2014/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84910016810&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84910016810&partnerID=8YFLogxK
U2 - 10.1111/cas.12487
DO - 10.1111/cas.12487
M3 - Article
C2 - 25060325
AN - SCOPUS:84910016810
VL - 105
SP - 1100
EP - 1108
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 9
ER -