TY - JOUR
T1 - Reduction of fatty acid oxidation and responses to hypoxia correlate with the progression of de-differentiation in HCC
AU - Tanaka, Masatake
AU - Masaki, Yuko
AU - Tanaka, Kosuke
AU - Miyazaki, Masayuki
AU - Kato, Masaki
AU - Sugimoto, Rie
AU - Nakamura, Kazuhiko
AU - Aishima, Shinichi
AU - Shirabe, Ken
AU - Nakamuta, Makoto
AU - Enjoji, Munechika
AU - Kotoh, Kazuhiro
AU - Takayanagi, Ryoichi
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013/2
Y1 - 2013/2
N2 - The prognosis of patients with hepatocellular carcinoma (HCC) may be improved by novel treatments focusing on the characteristic metabolic changes of this disease. Therefore, we analyzed the biological interactions of metabolic features with the degree of tumor differentiation and the level of malignant potential in 41 patients with completely resectable HCC. The expression levels in resected samples of mRNAs encoded by genes related to tumor metabolism and metastasis were investigated, and the correlation between these expression levels and degrees of differentiation was analyzed. Of the 41 patients, 2 patients had grade I, 27 had grade II, and 12 had grade III tumors. Reductions in the levels of 3-hydroxyacyl-CoA dehydrogenase (HADHA) and acyl-CoA oxidase (ACOX)-2 mRNAs, and increases in pyruvate kinase isoenzyme type M2 (PKM2) mRNA were significantly correlated with the progression of de-differentiation. Analysis of partial correlation coefficients showed that the level of PKM2 mRNA expression was significantly correlated with those of pro-angiogenic genes, vascular endothelial growth factor (VEGF) and ETS-1. Moreover, the levels of VEGF-A and ETS-1 mRNA expression were independently correlated with that of the epithelial-mesenchymal transition (EMT) related gene SNAIL. These findings suggest that reductions in fatty acid oxidation and responses to hypoxia may affect the progression of malignant phenotypes in HCC.
AB - The prognosis of patients with hepatocellular carcinoma (HCC) may be improved by novel treatments focusing on the characteristic metabolic changes of this disease. Therefore, we analyzed the biological interactions of metabolic features with the degree of tumor differentiation and the level of malignant potential in 41 patients with completely resectable HCC. The expression levels in resected samples of mRNAs encoded by genes related to tumor metabolism and metastasis were investigated, and the correlation between these expression levels and degrees of differentiation was analyzed. Of the 41 patients, 2 patients had grade I, 27 had grade II, and 12 had grade III tumors. Reductions in the levels of 3-hydroxyacyl-CoA dehydrogenase (HADHA) and acyl-CoA oxidase (ACOX)-2 mRNAs, and increases in pyruvate kinase isoenzyme type M2 (PKM2) mRNA were significantly correlated with the progression of de-differentiation. Analysis of partial correlation coefficients showed that the level of PKM2 mRNA expression was significantly correlated with those of pro-angiogenic genes, vascular endothelial growth factor (VEGF) and ETS-1. Moreover, the levels of VEGF-A and ETS-1 mRNA expression were independently correlated with that of the epithelial-mesenchymal transition (EMT) related gene SNAIL. These findings suggest that reductions in fatty acid oxidation and responses to hypoxia may affect the progression of malignant phenotypes in HCC.
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U2 - 10.3892/mmr.2012.1201
DO - 10.3892/mmr.2012.1201
M3 - Article
C2 - 23178736
AN - SCOPUS:84873820273
SN - 1791-2997
VL - 7
SP - 365
EP - 370
JO - Molecular medicine reports
JF - Molecular medicine reports
IS - 2
ER -
