Abstract
Aberrant glycosylation is not only a feature of malignant cell transformation, but also plays an important role in metastasis. In the present study, an integrated strategy combining the lectin microarrays and lectin cytochemistry was employed to investigate and verify the altered glycopatterns in gastric cancer (GC) cell lines as well as resected tumor specimens from matched tissue sets of 46 GC patients. Subsequently, lectin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS were employed to further acquire precise structural information of the altered glycans. According to the results, the glycopatterns recognized by 10 (e.g., ACA, MAL-I, and ConA) and 3 lectins (PNA, MAL-I, and VVA) showed significantly variations in GC cells and tissue compared to their corresponding controls, respectively. Notably, the relative abundance of Galβ-1,4GlcNAc (LacNAc) recognized by MAL-I exhibited a significant increase in GC cells (p < 0.001) and tissue from patients at stage II and III (p < 0.05), and a significant increase in lymph node positive tumor cases, compared with lymph node negative tumor cases (p < 0.05). More LacNAc contained N-glycans were characterized in tumor sample with advanced stage compared to corresponding control. Moreover, there were 10 neo-LacNAc-contained N-glycans (e.g., m/z 1625.605, 1803.652, and 1914.671) only presented in GC tissue with advanced stage. Among these, six N-glycans were modified with sialic acid or fucose based on LacNAc to form sialylated N-glycans or lewis antigens, respectively. Our results revealed that the aberrant expression of LacNAc is a characteristic of GC, and LacNAc may serve as a scaffold to be further modified with sialic acid or fucose. Our findings provided useful information for us to understand the development of GC.
Highlights
Gastric carcinoma (GC) is the third most common cause of cancer mortality in the world (1)
We found that the relative abundance of T antigen as well as LacNAc showed significantly increased in both gastric cancer (GC) cells and tissue from patients at stage II and III compared to their corresponding controls
Some studies reported that the high expressions of T antigen is highly associated with the metastatic and poor survival in prostate cancer and the interaction between galectin-4 and T antigen may contribute to this process (34, 35)
Summary
Gastric carcinoma (GC) is the third most common cause of cancer mortality in the world (1). Alterations of glycosylation are common features of some diseases such as cancer (9, 10). The level of sialylation is known to be elevated in various cancers (11, 12). The sialyl-Lewis X (SLex) epitope is a well-known tumor-associated carbohydrate antigen that is significantly increased on triantennary glycans and is accompanied by increased levels of core fucosylated agalactosyl biantennary glycans, which is present on IgG isolated from GC patients. Increased levels of these glycans are associated with increasing disease pathogenesis and liver metastasis, and the increased expression of SLex is a result of pro-inflammatory cytokine signaling during carcinogenesis (13, 14). The N-glycosylation of GC cell lines with various grades of differentiation (AGS, SGC-7901, and NCI-N87) were characterized and compared by ultra-high performance liquid chromatography (UHPLC), as a result, different levels of N-glycosylation were exhibited among GC cells (16)
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