title: The combination of the expression of hexokinase 2 and pyruvate kinase M2 is a prognostic marker in patients with pancreatic cancer.
abstract: Metabolism may determine the biologically malignant behavior of pancreatic cancer. To investigate the significance and prognostic value of cancer metabolism in cancer patients, we investigated the expression of two key enzymes in anaerobic glycolysis, hexokinase 2 (HK2) and pyruvate kinase isoenzyme type M2 (PKM2), in surgical specimens obtained from 36 patients who underwent curative resection of pancreatic ductal carcinoma. The hk2-glycolysis axis is a key system in the clinical imaging of tumors via positron emission tomography. Immunohistochemical staining for hk2 and pkm2 was performed and the data were statistically analyzed to evaluate their prognostic power. The expression of hk2 and pkm2 was associated with clinicopathological variables and patient prognosis, including overall survival, local recurrence-free survival and distant metastasis-free survival. Staining for hk2 was negative and positive in 42 and 58% of the patients, respectively, whereas staining for pkm2 was negative and positive in 56 and 44%, respectively; hk2-positive staining was correlated with progressive pathological tumor stage (pT3 vs. pT1 and pT2; P=0.017). In the univariate analysis, the positive expression of hk2 and pkm2, pathological stage (pT3 vs. pT1 and pT2) and nodal metastasis were significantly correlated with poor prognosis (P<0.03). In the multivariate analysis, pathological nodal metastasis was an independent prognostic factor for overall survival, whereas the positive expression of hk2 and pkm2 exhibited borderline significance (P=0.08 and 0.12, hazard ratio = 2.57 and 2.16, respectively). In addition, the combination of high expression of hk2 as well as pkm2 was found to be significant (P<0.05). These results suggested that the expression of hk2 and pkm2, particularly their combination, in surgical specimens obtained during curative resection, may predict an unfavorable clinical outcome in patients with pancreatic cancer.
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan ; Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Ogawa
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagano
authors.affiliation: Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Konno
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Eguchi
authors.affiliation: Department of Cancer Profiling Discovery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Koseki
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan ; Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kawamoto
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan ; Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Nishida
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Hugh
authors.initials: H
authors.lastname: Colvin
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Tomokuni
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Tomimaru
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hama
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wada
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Marubashi
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Kobayashi
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.affiliation: Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan ; Department of Cancer Profiling Discovery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Hideshi
authors.initials: H
authors.lastname: Ishii
keywords: cancer metabolism; hexokinase; pancreatic cancer; pyruvate kinase