Proteomic analysis for developing new biomarkers of hepatocellular carcinoma  

作　　者：Maria Pleguezuelo Laura M Lopez-Sanchez Antonio Rodriguez-Ariza Jose L Montero Javier Briceno Ruben Ciria Jordi Muntane Manuel de la Mata 

机构地区：[1]Liver Research Unit and Academic Department of Surgery, Reina Sofia University Hospital [2]Research Unit, Reina Sofia University Hospital [3]Liver Research Unit and Academic Department of Surgery, CIBERehd, Reina Sofia University Hospital

出　　处：《World Journal of Hepatology》2010年第3期127-135,共9页世界肝病学杂志（英文版）（电子版）

基　　金：Supported by the Centrode Investigacion Biomedicaen Reden Enfermedades Hepaticasy Digestivas (CIBERehd)

摘　　要：AIM: To identify new markers of hepatocellular carcinoma (HCC) using a proteomic analysis. METHODS: Patients with liver cirrhosis of the three most frequent etiologies: hepatitis C virus, hepatitis B virus and alcoholic liver disease, were included in the study. The samples were analysed by 2D-electrophoresis in order to determine the differential protein expression. The proteins were separated according to the charge in immobilized pH 3-10 gradient strips and then by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Proteins of interest were excised, digested with trypsin and the resulting peptides were separated and identified. RESULTS: Three differentially expressed apolipoproteins (Apo) were identified based on the protein profile using proteomic techniques: Apo-A1, Apo-A4 and Apo-E. Apo-A4 levels were significantly lower in HCC than in non-HCC patients regardless of etiology (P < 0.01). Multivariate logistic regression showed that Apo-A4 and Apo-A1 were the only independent factors related to HCC diagnosis (P < 0.05). The receiver operating characteristic (ROC) curve including both Apo-A4 and Apo-A1 showed an area under the ROC of 0.944 (P < 0.001), a sensitivity of 0.89 and a specificity of 0.81 for diagnosis of HCC. CONCLUSION: Apo-A4 and Apo-A1 may be used clinically as biomarkers of HCC with a high sensibility and specificity. These findings may provide additional insights into the mechanism of HCC development and progression.AIM: To identify new markers of hepatocellular carcinoma (HCC) using a proteomic analysis.METHODS: Patients with liver cirrhosis of the three most frequent etiologies: hepatitis C virus, hepatitis B virus and alcoholic liver disease, were included in the study. The samples were analysed by 2D-electrophoresis in order to determine the differential protein expression. The proteins were separated according to the charge in immobilized pH 3-10 gradient strips and then by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Proteins of interest were excised, digested with trypsin and the resulting peptides were separated and identified.RESULTS: Three differentially expressed apolipoproteins (Apo) were identified based on the protein profile using proteomic techniques: Apo-A1, Apo-A4 and Apo-E. Apo-A4 levels were significantly lower in HCC than in non-HCC patients regardless of etiology (P < 0.01). Multivariate logistic regression showed that Apo-A4 and Apo-A1 were the only independent factors related to HCC diagnosis (P < 0.05). The receiver operating characteristic (ROC) curve including both Apo-A4 and Apo-A1 showed an area under the ROC of 0.944 (P < 0.001), a sensitivity of 0.89 and a specificity of 0.81 for diagnosis of HCC.CONCLUSION: Apo-A4 and Apo-A1 may be used clinically as biomarkers of HCC with a high sensibility and specificity. These findings may provide additional insights into the mechanism of HCC development and progression.

关 键 词：Liver cancer APOLIPOPROTEINS Serum biomarkers 2D POLYACRYLAMIDE GEL ELECTROPHORESIS Mass SPECTROMETRY 

分 类 号：R735.7[医药卫生—肿瘤]