Abstract
Cancer progression is usually associated with alterations of glycan expression patterns. Little is known regarding global glycomics in gastric cancer, the most common type of epithelial cancer. We integrated lectin microarray and mass spectrometry (MS) methods to profile glycan expression in three gastric cancer cell lines (SGC-7901, HGC-27, and MGC-803) and one normal gastric epithelial cell line (GES-1). Significantly altered glycans were confirmed by lectin staining and MALDI-TOF/TOF-MS. The three cancer cell lines showed increased levels of core-fucosylated N-glycans, GalNAcα-Ser/Thr (Tn antigen), and Sia2-6Galβ1-4GlcNAc N-glycans, but reduced levels of biantennary N-glycans, Galβ1-3GalNAcα-Ser/Thr (T antigen), and (GlcNAc)n N-glycans. Lectin histochemistry was used to validate aberrant expression of four representative glycans (core-fucosylation, Sia2-6Galβ1-4GlcNAc, biantennary N-glycans, T antigen, recognized respectively by lectins LCA, SNA, PHA-E+L, and ACA) in clinical gastric cancer samples. Lower binding capacity for ACA was correlated with significantly poorer patient prognosis. Our findings indicate for the first time that glycans recognized by LCA, ACA, and PHA-E+L are aberrantly expressed in gastric cancer, and suggest that ACA is a potential prognostic factor for gastric cancer.
Highlights
Gastric cancer is a common epithelial cancer and the second leading cause of cancer death worldwide [1, 2]
Our findings indicate for the first time that glycans recognized by LCA, ACA, and PHA-E+L are aberrantly expressed in gastric cancer, and suggest that ACA is a potential prognostic factor for gastric cancer
Significant differences of glycans recognized by 10 different lectins were observed for cancer cells in comparison with normal cells (Figure 1)
Summary
Gastric cancer is a common epithelial cancer and the second leading cause of cancer death worldwide [1, 2]. In China, ~400,000 new cases of gastric cancer and ~300,000 deaths from the disease were reported during 2005-2010, making it the second most common type of cancer [3, 4]. New prognostic biomarkers are needed to facilitate early diagnosis of cancer, improve treatment outcome, and prolong patient survival. More reliable tissue or serum biomarkers for early diagnosis of gastric cancer are highly desirable. Glycosylation is a common post-translational modification estimated to occur in >70% of human proteins [6]. It plays crucial roles in molecular recognition, cell-cell adhesion, molecular trafficking, receptor activation, signal transduction, and endocytosis [7]. Aberrant protein glycosylation often occurs during malignant transformation, leads to formation of specific tumor-associated glycans, and is associated with tumor invasiveness, metastasis, and overall poor prognosis [8, 9]
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