-Glycan and Glycopeptide Serum Biomarkers in Philippine Lung Cancer Patients Identified Using Liquid Chromatography-Tandem Mass Spectrometry.

Aberrant glycosylation has been extensively reported in cancer, with fundamental changes in the glycosylation patterns of cell-surface and secreted proteins largely occurring during cancer progression. As such, serum glycan and glycopeptide biomarkers have been discovered using mass spectrometry and proposed for cancer detection. Here, we report for the first time potential serum -glycan and glycopeptide biomarkers for Philippine lung cancer patients. The -glycan and glycoprotein profiles of a cohort ( = 26 patients, = 22 age- and gender-matched) of lung cancer patients were analyzed and compared to identify potential -glycan and glycopeptide serum biomarkers using nano-QToF-MS/MS and ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry dynamic multiple monitoring methods, respectively. Statistical analyses identified differential -glycan and glycopeptide abundances. The -glycans were mostly sialylated and sialofucosylated branched structures. The glycopeptides involved proteins in complement and coagulation cascades ( 6.418 × 10), innate immunity ( 6.094 × 10), acute inflammatory response ( 6.404 × 10), defense response ( 2.082 × 10), complement activation pathways ( 1.895 × 10), and immunoglobulin-mediated immune response pathways ( 4.818 × 10). Biomarker models were constructed using serum -glycans [area under the curve (AUC) = 0.775; 95% CI: 0.617-0.931] and glycopeptides (AUC = 0.959; 95% CI: 0.85-1.0), with glycopeptides having higher accuracies than -glycans. The results suggest that in the Philippine lung cancer patient sera, specific -glycans and site-specific glycans are differentially expressed between cases and controls. This report represents the first serum glycan and glycopeptide biomarkers of Philippine lung cancer patients, further demonstrating the utility of mass spectrometry-based glycomic and glycoproteomic methods.