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World J Hepatol. 2010 Mar 27;2(3):127-35. doi: 10.4254/wjh.v2.i3.127.

Proteomic analysis for developing new biomarkers of hepatocellular carcinoma.

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  • 1Maria Pleguezuelo, Ruben Ciria, Liver Research Unit and Academic Department of Surgery, Reina Sofia University Hospital, Avda Menendez Pidal s/n, Cordoba 14004, Spain.



To identify new markers of hepatocellular carcinoma (HCC) using a proteomic analysis.


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.


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.


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.


2D polyacrylamide gel electrophoresis; Apolipoproteins; Liver cancer; Mass spectrometry; Serum biomarkers

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