earticle

영어

Gastric cancer is one of the most common malignancy and leading cause of cancer death. Classically, CEA and CA19-9 have been used for gastric cancer detection. However, CEA and CA19-9 insufficient for cancer detection due to low specificity and sensitivity. Glycosylation is the most common post-translational modification and plays an important role in various biological processes. Whole serum based glycan profiling has been already developed and widely used in cancer biomarker study. While, targeted glycoproteomic approach is needed in clinic for better sensitivity and specificity. In previous study, we targeted serum haptoglobin for gastric cancer. We found glycosylation changes of haptoglobin on released N-glycan between gastric cancer patient and healthy control. Released glycan analysis provide compositional and isomer information while cannot give actual site of glycosylation. On the other hand, intact glycopeptide analysis provide site-specific information. Based on this actual glycosylation site and glycan heterogeneity, we monitored more detailed glycan changes and aberrant glycosylation of each site for more sensitive and specific diagnosis. In this study, we have developed the method for intact glycopeptide analysis for biomarker discovery using UHPLC MS. We successfully separated 3 glycopeptides and profiled the glycoform of 2 glycopeptides. The other one was difficult to profile glycoform according to two glycosylation sites. Therefore, this glycopeptide was fractionated and analyzed by nano LC chip Q-TOF MS. Further, cancer patient (n=40, stage IV) and healthy control (n=47) samples were applied for training set of biomarker study. A T-test based analysis was performed to identify potential biomarker (p<0.001). In the future, we will apply this platform to large clinical sample to validate potential biomarker.