Alterations in glycosylation of salivary proteins are associated with many diseases and are a common feature of cancer pathogenesis. Lung cancer is a malignant tumor with altered glycosylation during tumorigenesis and metastasis. Here, we collected saliva from different stages of patients with lung cancer (LC), healthy controls (HC) and other non-cancer disease (OD), and used MALDI-TOF/MS and LC-MS to comprehensively characterize differences of glycosylation. To analyze protein glycosylation, we used chemoenzymatic solid-phase methods to investigate changes in LC, HC and OD (<b>Figure 1</b>). Our preliminary results suggest that more than one fucose is present in most N-glycans. To determine the linkage of fucose, we subsequentially digested fucose on solid phase using different linkage-specific fucosidases. Finally, we develop a novel method to enrich core fucosylated and branched fucosylated glycoproteins.<br/>The results showed that fucosylated N-glycans were substantially upregulated in LC, and more so in advanced lung cancer. In addition to core fucosylation, linkage analysis of complex N-glycans revealed the presence of multiple fucoses on either antenna-GlcNAc (a1,3) or antenna-Gal (a1-2). These hyper-fucosylations were significantly increased in the LC, while the core-fucosylation of high-mannose had negligible changes in the LC. However, the changes in the hybrid glycans were remarkably reduced in the LC. Site-specific N-glycosylation analysis identified 57 glycoproteins specifically present in LC. Considering the fact that fucosylation is concurrently regulated by fucosidases and FUTs, we analyzed specific FUTs that synthesize a1-2 and a1-3 fucoses. Analysis of clinical specimens from tumors and adjacent non-tumor tissues found that FUT3 and FUT9 may be key enzymes for hyper-fucosylation in salivary glycoproteins. In addition, we will characterize the early tumor-specific fucosylation (TSF), which can serve as a cancer biomarker for early detection.

Elevated salivary fucosylation is associated with stage in lung cancer patients

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