Liquid chromatography mass spectrometry-based O-glycomics to evaluate glycosylation alterations in gastric cancer

Abstract

Purpose: Gastric cancer is the fourth most common malignant cancer worldwide. Important for tumorigenesis and progression, aberrant glycosylation occurs frequently in cancers. We investigated the differences in O-glycosylation in the serum of 157 gastric cancer patients (GC) and 144 healthy donors.

Experimental design: We used the method of labeling O-glycans (released from proteins) with 1-phenyl-3-methyl-5-pyrazolone followed by LC-MS analysis. Analyzing the LC-MS data by partial least squares discriminant and unpaired Student t test, combined with the structural information of O-glycans from LC-MS/MS in positive mode.

Results: The expression level of core1, core2, ST antigen, and core2 complex O-glycans (m/z 733.33, m/z 809.42) were increased significantly (p < 0.0001), whereas m/z 529.75 and diST-antigen were decreased in the serum of GC compared with controls (p < 0.001). In addition, there were significant correlations between the abundance of the O-glycans and glycoproteins (MUC1, CEA) in the serum of GC.

Conclusion and clinical relevance: Glycomics approaches identified multiple candidate antigens for patients with GC. The O-glycan structures are increased in the serum of GC, they may be candidates for carbohydrate tumor markers.

Keywords: 1-Phenyl-3-methyl-5-pyrazolone; Gastric cancer; LC-MS; O-glycan; Serum.