Overexpression of alpha enolase in hepatitis C virus-related hepatocellular carcinoma: association with tumor progression as determined by proteomic analysis.
To identify proteins that could be molecular targets for diagnosis and treatment of hepatitis C virus-related hepatocellular carcinoma (HCV-related HCC), we used a proteomic approach to analyze protein expression in samples of human liver. Twenty-six pairs of tumorous and corresponding nontumorous liver samples from patients with HCV-related HCC and six normal liver samples were analyzed by two-dimensional gel electrophoresis and liquid chromatography-tandem mass spectrometry. One of the numerous spots that showed stronger intensity in tumorous than in nontumorous samples was identified as alpha enolase, a key enzyme in the glycolytic pathway. Expression of this protein increased with tumor dedifferentiation and was significantly higher in poorly differentiated HCC than in well-differentiated HCC. This pattern was reproduced by immunoblot analysis and immunohistochemistry. Expression of alpha enolase also correlated positively with tumor size and venous invasion. These results suggest that alpha enolase is one of the candidates for biomarkers for tumor progression that deserves further investigation in HCV-related HCC.
Takashima
Motonari
M
Department of Surgery II, Yamaguchi University School of Medicine, Ube, Japan.
Kuramitsu
Yasuhiro
Y
Yokoyama
Yuichiro
Y
Iizuka
Norio
N
Fujimoto
Masanori
M
Nishisaka
Takashi
T
Okita
Kiwamu
K
Oka
Masaaki
M
Nakamura
Kazuyuki
K
D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D002853:Chromatography, Liquid; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006526:Hepatitis C; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D010751:Phosphopyruvate Hydratase / Q000096:biosynthesis*; D040901:Proteomics; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase