Journal of Chromatography & Separation Techniques
Open Access

Core-fucosylated glycopeptides in hepatocellular carcinoma

3^rd International Conference on Mass Spectrometry

October 10-11, 2016 Kuala Lumpur, Malaysia

Haidi Yin

The Hong Kong Polytechnic University, Hong Kong

Posters & Accepted Abstracts: J Chromatogr Sep Tech

Abstract :

Aberrant core-fucosylation (CF) is often associated with the development of hepatocellular carcinoma (HCC). A mass spectrometry-based methodology has been developed to study changes of site-specific CF of target candidate proteins as well as of non-target serum proteins among cirrhosis and HCC samples. The methods involve trypsin digestion, enrichment of CF peptides, followed by glycan truncation while retaining the innermost N-acetylglucosamine (GlcNAc) and/or core-fucose bound to the peptide. Ceruloplasmin, one of the target proteins was found to be up-regulated in the early stage alcohol-related HCC serum samples compared with alcohol-related cirrhosis samples but not in HBV or HCV-related samples. Four CF sites (sites 138, 358, 397 and 762) were present in ceruloplasmin, among which the core-fucosylation level of sites 138 and 397 were more susceptible to change in disease states. Most interestingly, the CF level of 3 sites of ceruloplasmin increased significantly in alcohol-related HCC samples compared to alcohol-related cirrhosis samples, with the highest AUC (area under the curve) value of 0.838 at site 138. Large scale mass spectrometry-based screening quantified 1300 CF peptides where 20 CF peptides were differentially expressed in alcoholrelated HCC samples compared with alcohol-related cirrhosis samples and 26 CF peptides changed in HCV-related HCC samples compared to HCV-related cirrhosis samples. Among these, we found three CF peptides from fibronectin upregulated in alcoholrelated HCC samples compared with alcohol-related cirrhosis samples with an AUC value of 0.89 at site 1007 with a specificity of 85.7% at a sensitivity of 92.9% (generated with 10-fold cross-validation). When combined with the AFP index, the AUC value reached to 0.92 with a specificity of 92.9% at a sensitivity of 100%, it significantly improved compared to that with AFP alone (LR test p <0.001).

Biography :

Email: haidi.yin@polyu.edu.hk