title: Reduction of fatty acid oxidation and responses to hypoxia correlate             with the progression of de-differentiation in HCC.
abstract: 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.
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School                     of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582,                     Japan.
authors.forename: Masatake
authors.initials: M
authors.lastname: Tanaka
authors.forename: Yuko
authors.initials: Y
authors.lastname: Masaki
authors.forename: Kosuke
authors.initials: K
authors.lastname: Tanaka
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Masaki
authors.initials: M
authors.lastname: Kato
authors.forename: Rie
authors.initials: R
authors.lastname: Sugimoto
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Shinichi
authors.initials: S
authors.lastname: Aishima
authors.forename: Ken
authors.initials: K
authors.lastname: Shirabe
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamuta
authors.forename: Munechika
authors.initials: M
authors.lastname: Enjoji
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kotoh
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Takayanagi
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D000860:Hypoxia; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D015094:3-Hydroxyacyl CoA Dehydrogenases; D002352:Carrier Proteins; D005227:Fatty Acids; D008565:Membrane Proteins; D010088:Oxidoreductases; D050784:Proto-Oncogene Protein c-ets-1; D012333:RNA, Messenger; D000071250:Snail Family Transcription Factors; D013963:Thyroid Hormones; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D000097810:Thyroid Hormone-Binding Proteins; C494041:ETS1 protein, human; C576470:ACOX2 protein, human