Hexokinase 2 in colorectal cancer: a potent prognostic factor associated with glycolysis, proliferation and migration
Munetoshi Katagiri1,2, Hideaki Karasawa1, Kiyoshi Takagi3, Shun Nakayama1, Shinichi Yabuuchi1, Fumiyoshi Fujishima2, Takeshi Naitoh1, Mika Watanabe2, Takashi Suzuki3, Michiaki Unno1 and Hironobu Sasano2,4
Departments of 1Surgery, 3Pathology and Histotechnology, 4Anatomic Pathology, Tohoku University Graduate School of Medicine and 2Department of Pathology, Tohoku University Hospital, Sendai, Japan
Offprint requests to: Takashi Suzuki, MD, PhD., Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine. 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi-ken, 980-8575 Japan. e-mail: t-suzuki@patholo2.med.tohoku.ac.jp
Summary. Background: It is well known that proliferating carcinoma cells preferentially use aerobic glycolysis rather than oxidative phosphorylation for energy production. Hexokinase 2 (HK2) plays a pivotal role in the glycolytic pathway. Previous studies have demonstrated that HK2 activity is markedly increased in various malignant neoplasms, but the clinical and biological significance of HK2 remain largely unclear in the colorectal carcinoma.
Patients and methods: We performed immunohisto-chemistry for HK2 in 195 colorectal carcinoma tissues. We also used HCT8 and HT29 colon carcinoma cells in in vitro studies.
Results: HK2 immunoreactivity was detected in 100 out of 195 (51%) colorectal carcinoma tissues, and the immunohistochemical HK2 status was significantly associated with tumor size, depth of invasion, liver metastasis and TNM stage in these cases. Moreover, the HK2 status was significantly associated with increased incidence of recurrence and overall mortality of the patients, and multivariate analyses demonstrated that HK2 status was an independent prognostic factor for both disease-free and overall survival. Subsequent in vitro experiments revealed that both HCT8 and HT29 colon carcinoma cells transfected with specific siRNA for HK2 significantly decreased the lactate production, proliferation activity and migration property.
Conclusion: These results suggest that HK2 plays important roles in the glycolytic, proliferation and migration properties of colorectal carcinoma and, therefore, HK2 status is a potent worse prognostic factor in colorectal cancer patients. Histol Histopathol 32, 351-360 (2017)
Key words: Colorectal cancer, Immunohistochemistry, Invasion, Prognosis, Proliferation
DOI: 10.14670/HH-11-799