Tongue Cancer Patients Can be Distinguished from Healthy Controls by Specific N ‐Glycopeptides Found in Serum

Purpose There are no blood biomarkers to detect early‐stage oral cavity squamous cell carcinoma (OSCC) prior to clinical signs. Most OSCC incidence is associated with significant morbidity and poor survival. The authors aimed to use mass‐spectrometry (MS) technology to find specific N ‐glycopeptides potentially serving as serum biomarkers for preclinical OSCC screening. Experimental design Serum samples from 14 patients treated for OSCC (stage I or stage IV) with 12 age‐ and sex‐matched controls are collected. Quantitative label‐free N ‐glycoproteomics is performed, with MS/MS analysis of the statistically significantly different N ‐glycopeptides. Results Combined with a database search using web‐based software (GlycopeptideID), MS/MS provided detailed N ‐glycopeptide information, including glycosylation site, glycan composition, and proposed structures. Thirty‐eight tryptic N ‐glycopeptides are identified, having 19 unique N ‐glycosylation sites representing 14 glycoproteins. OSCC patients, including stage I tumors, can be differentiated from healthy controls based on the expression levels of these glycoforms. N ‐glycopeptides of IgG1, IgG4, haptoglobin, and transferrin have statistically significant different abundances between cases and controls. Conclusions and clinical relevance The authors are the first to suggest specific N ‐glycopeptides to serve as potential serum biomarkers to detect preclinical OSCC in patients. These N ‐glycopeptides are the lead candidates for validation as future diagnostic modalities of OSCC as early as stage I.