The principal aim of the present study consisted in the identification of the disregulated proteins associated with the development of hepatocellular carcinoma (HCC). The differences in protein expression between hepatocellular carcinoma (HCC) and the corresponding non-HCC liver tissues were investigated in a cohort of 20 patients using two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS). The up- and down-regulated protein spots that exhibited 1.5-fold difference signal intensity with statistical significance (p<0.05, t-test, confidence intervals 95%) were excised from the gel and identified by peptide mass fingerprinting using matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Thirty-six protein spots corresponding to 29 different disregulated proteins, belonging to heterogeneous metabolic pathways, have been identified. Down-regulated proteins (n=23) were found superior in number than the up-regulated proteins (n=6). Detoxification, carbohydrate metabolism and amino acid biotrasformation represented the main disregulated pathways in HCC. Up-regulation of aldo-keto reductase 1C2, thioredoxin and transketolase, involved in metabolic and regulatory cellular processes including proliferation, differentiation and carcinogenesis were remarkable. These proteins could represent useful biomarkers to provide new insights into global pathophysiologic changes of HCC and for the development of new pharmacological approaches to HCC therapy.

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