785 SORAFENIB PLUS OCTREOTIDE IN ADVANCED HEPATOCELLULAR CARCINOMA: UPDATED RESULTS OF A MULTICENTER STUDY

Hepatocellular carcinoma (HCC) is one of the leading causes of cancerrelated death worldwide.To identify biomarkers of hepatocellular carcinoma, we performed comparative proteomic analysis in five pairs of HCC tissue and the surrounding non-tumor tissue.Among differentially expressed proteins, 54 up-regulated protein spots (ratio tumor/ nontumor 1.5) and 32 down-regulated protein spots (ratio nontumor/ tumor 1.5) were identified by MALDI-TOF analysis.Finally, four novel biomarkers including the two up-regulated proteins (apolipoprotein E and 14-3-3 protein theta) and two down-regulated proteins (sulfortransferase 1 and methionine adenosyltransferase I) were further validated by western blot analysis in 50 pairs of HCC tissue and adjacent non-tumor tissue.The sensitivity and specificity of each biomarker protein for the detection of HCC were 54.9% and 94.1% for apolipoprotein E, 72.5% and 70.6% for 14-3-3 protein theta, 92.2% and 74.5% for sulfortransferase 1, and 75.0% and 63.5% for methionine adenosyltransferase, respectively.Combination of the individual markers improved the sensitivity and specificity up to 92.2% and 96.1%.Clinically, there was a positive correlation between up-regulation of 14-3-3 protein theta and venous invasion (p = 0.014) that may indicate a poor prognostic outcome.Furthermore, overexpression of 14-3-3 protein theta was associated with the resistance to anticancer druginduced apoptosis in HCC cell lines.Conclusion: Global protein profiling by proteomics allowed us to identify four candidate proteins as novel biomarkers for HCC and may provide insight into the mechanism of HCC carcinogenesis.