title: Combined evaluation of hexokinase 2 and phosphorylated pyruvate dehydrogenase-E1α in invasive front lesions of colorectal tumors predicts cancer metabolism and patient prognosis.
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.
authors: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors: Atsushi
authors: A
authors: Hamabe
authors: Hirofumi
authors: H
authors: Yamamoto
authors: Masamitsu
authors: M
authors: Konno
authors: Mamoru
authors: M
authors: Uemura
authors: Junichi
authors: J
authors: Nishimura
authors: Taishi
authors: T
authors: Hata
authors: Ichiro
authors: I
authors: Takemasa
authors: Tsunekazu
authors: T
authors: Mizushima
authors: Naohiro
authors: N
authors: Nishida
authors: Koichi
authors: K
authors: Kawamoto
authors: Jun
authors: J
authors: Koseki
authors: Yuichiro
authors: Y
authors: Doki
authors: Masaki
authors: M
authors: Mori
authors: Hideshi
authors: H
authors: Ishii
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D000368:Aged; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006593:Hexokinase / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology / Q000473:pathology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000201:enzymology*; D010750:Phosphoproteins / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D030481:Pyruvate Dehydrogenase (Lipoamide) / Q000378:metabolism*
chemical_list: D010750:Phosphoproteins; D030481:Pyruvate Dehydrogenase (Lipoamide); C065640:pyruvate dehydrogenase E1alpha subunit; D006593:Hexokinase
keywords: Colorectal cancer; hexokinase; invasion; metastasis; pyruvate dehydrogenase