Identification of serum N-glycans signatures in three major gastrointestinal cancers by high-throughput N-glycome profiling

Alternative N-glycosylation of serum proteins has been observed in colorectal cancer (CRC), esophageal squamous cell carcinoma (ESCC) and gastric cancer (GC), while comparative study among those three cancers has not been reported before. We aimed to identify serum N-glycans signatures and introduce a discriminative model across the gastrointestinal cancers. The study population was initially screened according to the exclusion criteria process. Serum N-glycans profiling was characterized by a high-throughput assay based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Diagnostic model was built by random forest, and unsupervised machine learning was performed to illustrate the differentiation between the three major gastrointestinal (GI) cancers. We have found that three major gastrointestinal cancers strongly associated with significantly decreased mannosylation and mono-galactosylation, as well as increased sialylation of serum glycoproteins. A highly accurate discriminative power (> 0.90) for those gastrointestinal cancers was obtained with serum N-glycome based predictive model. Additionally, serum N-glycome profile exhibited distinct distributions across GI cancers, and several altered N-glycans were hyper-regulated in each specific disease. Serum N-glycome profile was differentially expressed in three major gastrointestinal cancers, providing a new clinical tool for cancer diagnosis and throwing a light upon the disease-specific molecular signatures.