title: Novel glycan biomarkers for the detection of lung cancer.
abstract: Lung cancer has a poor prognosis and a 5-year survival rate of 15%. Therefore, early detection is vital. Diagnostic testing of serum for cancer-associated biomarkers is a noninvasive detection method. Glycosylation is the most frequent post-translational modification of proteins and it has been shown to be altered in cancer. In this paper, high-throughput HILIC technology was applied to serum samples from 100 lung cancer patients, alongside 84 age-matched controls and significant alterations in N-linked glycosylation were identified. Increases were detected in glycans containing Sialyl Lewis X, monoantennary glycans, highly sialylated glycans and decreases were observed in core-fucosylated biantennary glycans, with some being detectable as early as in Stage I. The N-linked glycan profile of haptoglobin demonstrated similar alterations to those elucidated in the total serum glycome. The most significantly altered HILIC peak in lung cancer samples includes predominantly disialylated and tri- and tetra-antennary glycans. This potential disease marker is significantly increased across all disease groups compared to controls and a strong disease effect is visible even after the effect of smoking is accounted for. The combination of all glyco-biomarkers had the highest sensitivity and specificity. This study identifies candidates for further study as potential biomarkers for the disease.
authors.affiliation: Department of Biochemistry, Oxford Glycobiology Institute, University of Oxford, South Parks Road, Oxford OX1 3QU, England.
authors.forename: James N
authors.initials: JN
authors.lastname: Arnold
authors.forename: Radka
authors.initials: R
authors.lastname: Saldova
authors.forename: Marie C
authors.initials: MC
authors.lastname: Galligan
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Murphy
authors.forename: Yuka
authors.initials: Y
authors.lastname: Mimura-Kimura
authors.forename: Jayne E
authors.initials: JE
authors.lastname: Telford
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Godwin
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Rudd
mesh_terms: D000837:Anion Exchange Resins / Q000737:chemistry; D014408:Biomarkers, Tumor / Q000097:blood* / Q000737:chemistry*; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002853:Chromatography, Liquid / Q000379:methods; D006023:Glycoproteins / Q000097:blood* / Q000737:chemistry*; D006031:Glycosylation; D006242:Haptoglobins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000737:chemistry; D008175:Lung Neoplasms / Q000097:blood / Q000737:chemistry* / Q000175:diagnosis*; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000032:analysis*; D012372:ROC Curve; D012680:Sensitivity and Specificity
chemical_list: D000837:Anion Exchange Resins; D014408:Biomarkers, Tumor; D006023:Glycoproteins; D006242:Haptoglobins; D007983:Lewis Blood Group Antigens; D011134:Polysaccharides