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

Abstract

Background 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 major gastrointestinal cancers has not been reported before. We aimed to identify cancer-specific serum N-glycan signatures and introduce a discriminative model between cancers in the same system. Methods The study population was initially screened according to the exclusion criteria process. Serum N-glycan 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. Results 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 was differentially distributed among those three cancer groups, and several altered N-glycans were unique to the specific cancer type. Conclusions 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 cancer-specific molecular signatures.