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

Cancer Science

Atsushi Hamabe²  Hirofumi Yamamoto²  Masamitsu Konno¹  Mamoru Uemura²  Junichi Nishimura²  Taishi Hata²  Ichiro Takemasa²  Tsunekazu Mizushima²  Naohiro Nishida¹  Koichi Kawamoto²  Jun Koseki³  Yuichiro Doki²  Masaki Mori² 

[1] Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Osaka, Japan;Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan;Department ofCancer Profiling Discovery, Graduate School of Medicine, Osaka University, Osaka, Japan

关键词: Colorectal cancer;    hexokinase;    invasion;    metastasis;    pyruvate dehydrogenase;   

DOI  :  10.1111/cas.12487

来源: Wiley

【 摘 要 】

Abstract

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.

【 授权许可】

CC BY-NC-ND   
© 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.