title: Comprehensive native glycan profiling with isomer separation and quantitation for the discovery of cancer biomarkers.
abstract: Glycosylation is highly sensitive to the biochemical environment and has been implicated in many diseases including cancer. Glycan compositional profiling of human serum with mass spectrometry has already identified potential biomarkers for several types of cancer and diseases; however, composition alone does not fully describe glycan stereo- and regioisomeric diversity. The vast structural heterogeneity of glycans presents a formidable analytical challenge. We have developed a method to identify and quantify isomeric native glycans using nanoflow liquid chromatography (nano-LC)/mass spectrometry. A microfluidic chip packed with graphitized carbon was used to chromatographically separate the glycans. To determine the utility of this method for structure-specific biomarker discovery, we analyzed serum samples from two groups of prostate cancer patients with different prognoses. More than 300 N-glycan species (including isomeric structures) were identified, corresponding to over 100 N-glycan compositions. Statistical tests established significant differences in glycan abundances between patient groups. This method provides comprehensive, selective, and quantitative glycan profiling.
authors.affiliation: Department of Chemistry, University of California, Davis, 95616, USA.
authors.forename: Serenus
authors.initials: S
authors.lastname: Hua
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: An
authors.forename: Sureyya
authors.initials: S
authors.lastname: Ozcan
authors.forename: Grace S
authors.initials: GS
authors.lastname: Ro
authors.forename: Stephanie
authors.initials: S
authors.lastname: Soares
authors.forename: Ralph
authors.initials: R
authors.lastname: DeVere-White
authors.forename: Carlito B
authors.initials: CB
authors.lastname: Lebrilla
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D006108:Graphite / Q000737:chemistry; D006801:Humans; D007536:Isomerism; D008297:Male; D013058:Mass Spectrometry; D046210:Microfluidic Analytical Techniques / Q000379:methods*; D036103:Nanotechnology / Q000379:methods; D011134:Polysaccharides / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D011134:Polysaccharides; D006108:Graphite