PMID- 25060325
OWN - NLM
STAT- MEDLINE
DCOM- 20141117
LR  - 20211021
IS  - 1349-7006 (Electronic)
IS  - 1347-9032 (Print)
IS  - 1347-9032 (Linking)
VI  - 105
IP  - 9
DP  - 2014 Sep
TI  - Combined evaluation of hexokinase 2 and phosphorylated pyruvate dehydrogenase-E1alpha 
      in invasive front lesions of colorectal tumors predicts cancer metabolism and 
      patient prognosis.
PG  - 1100-8
LID - 10.1111/cas.12487 [doi]
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-E1alpha (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.
CI  - (c) 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on 
      behalf of Japanese Cancer Association.
FAU - Hamabe, Atsushi
AU  - Hamabe A
AD  - Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka 
      University, Osaka, Japan.
FAU - Yamamoto, Hirofumi
AU  - Yamamoto H
FAU - Konno, Masamitsu
AU  - Konno M
FAU - Uemura, Mamoru
AU  - Uemura M
FAU - Nishimura, Junichi
AU  - Nishimura J
FAU - Hata, Taishi
AU  - Hata T
FAU - Takemasa, Ichiro
AU  - Takemasa I
FAU - Mizushima, Tsunekazu
AU  - Mizushima T
FAU - Nishida, Naohiro
AU  - Nishida N
FAU - Kawamoto, Koichi
AU  - Kawamoto K
FAU - Koseki, Jun
AU  - Koseki J
FAU - Doki, Yuichiro
AU  - Doki Y
FAU - Mori, Masaki
AU  - Mori M
FAU - Ishii, Hideshi
AU  - Ishii H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140916
PL  - England
TA  - Cancer Sci
JT  - Cancer science
JID - 101168776
RN  - 0 (Phosphoproteins)
RN  - EC 1.2.4.1 (Pyruvate Dehydrogenase (Lipoamide))
RN  - EC 1.2.4.1 (pyruvate dehydrogenase E1alpha subunit)
RN  - EC 2.7.1.1 (Hexokinase)
SB  - IM
MH  - Adenocarcinoma/*enzymology/mortality/pathology
MH  - Aged
MH  - Cell Line, Tumor
MH  - Colorectal Neoplasms/*enzymology/mortality/pathology
MH  - Disease-Free Survival
MH  - Female
MH  - Hexokinase/*metabolism
MH  - Humans
MH  - Intestinal Mucosa/enzymology/pathology
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Middle Aged
MH  - Multivariate Analysis
MH  - Neoplasm Invasiveness
MH  - Neoplasm Recurrence, Local/*enzymology
MH  - Phosphoproteins/metabolism
MH  - Protein Processing, Post-Translational
MH  - Pyruvate Dehydrogenase (Lipoamide)/*metabolism
PMC - PMC4462394
OTO - NOTNLM
OT  - Colorectal cancer
OT  - hexokinase
OT  - invasion
OT  - metastasis
OT  - pyruvate dehydrogenase
EDAT- 2014/07/26 06:00
MHDA- 2014/11/18 06:00
PMCR- 2014/09/01
CRDT- 2014/07/26 06:00
PHST- 2014/03/10 00:00 [received]
PHST- 2014/06/22 00:00 [revised]
PHST- 2014/07/04 00:00 [accepted]
PHST- 2014/07/26 06:00 [entrez]
PHST- 2014/07/26 06:00 [pubmed]
PHST- 2014/11/18 06:00 [medline]
PHST- 2014/09/01 00:00 [pmc-release]
AID - 10.1111/cas.12487 [doi]
PST - ppublish
SO  - Cancer Sci. 2014 Sep;105(9):1100-8. doi: 10.1111/cas.12487. Epub 2014 Sep 16.