Altered desialylated plasma N-glycan profile in patients with non-small cell lung carcinoma

Article type: Research Article

Authors: Bartling, Babett^{a; *; 1} | Vanhooren, Valerie^{b; c; 1} | Dewaele, Sylviane^{b; c} | Libert, Claude^{b; c} | Hofmann, Hans-Stefan^d | Haerting, Johannes^e | Nuding, Sebastian^f | Silber, Rolf-Edgar^a | Simm, Andreas^a | Chen, Cuiying Chitty^{b; c; *}

Affiliations: [a] Department of Cardio-thoracic Surgery, University Hospital Halle (Saale), Martin Luther University Halle-Wittenberg, Halle (Saale), Germany | [b] Department for Molecular Biomedical Research, VIB, Ghent, Belgium | [c] Department of Biomedical Molecular Research, Ghent University, Ghent, Belgium | [d] Department of Thoracic Surgery, Hospital Barmherzige Brüder Regensburg, Regensburg, Germany | [e] Institute of Medical Epidemiology, Biostatistics and Informatics, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany | [f] Department of Medicine III, University Hospital Halle (Saale), Martin Luther University Halle-Wittenberg, Halle (Saale), Germany

Correspondence: [*] Corresponding authors: Babett Bartling, Klinik für Herz- und Thoraxchirurgie, Universitätsklinikum Halle (Saale), Ernst-Grube-Straße 40, 06120 Halle (Saale), Germany. Tel.: +49 345 557 3314; Fax: +49 345 557 7070; E-mail: babett.bartling@uk-halle.de. Department for Molecular Biomedical Research, VIB and Department of Biomedical Molecular Research, Ghent University, Technologiepark 927, 9052 Gent, Belgium. Tel.: +32 93313702; Fax: +32 93313609; E-mail: chitty@dmbr.ugent.be E-mail: babett.bartling@uk-halle.de. Department for Molecular Biomedical Research, VIB and Department of Biomedical Molecular Research, Ghent University, Technologiepark 927, 9052 Gent, Belgium. Tel.: +32 93313702; Fax: +32 93313609; E-mail: chitty@dmbr.ugent.be.

Note: [1] Contributed equally.

Abstract: Successful therapy of the non-small cell lung carcinoma (NSCLC) depends on its early detection, and non-invasive detection methods are preferred. As plasma proteins are modified by N-linked glycosylation, we tested the importance of the N-glycan profile in diagnosing and prognosticating NSCLC. We analysed desialylated plasma samples from 75 NSCLC patients, and 71 healthy individuals by the high-throughput DNA sequencer-based carbohydrate analytical profiling technique. We detected alterations in the levels of several N-glycans in NSCLC patients. Total α-1,6-core fucosylated biantennaries (NGA2F, NG1A2F, NA2F) and total bisecting α-1,6-core fucosylated biantennaries (NGA2FB, NA2FB) were reduced in NSCLC patients, whereas the branching α-1,3-fucosylated triantennary N-glycan (NA3FB) was increased. Best diagnostic accuracy was identified for NG1A2F. NSCLC patients with TNM stage I stage did not show further differences, but patients with higher stages did (TNM II to IV). Those patients additionally had a reduced level in the α-1,6-core fucosylated structure NA2F with parallel increase in the non-fucosylated structure NA2. In this regard, NSCLC patients with a relatively low amount of NA2 per NA2F had a better three-year survival than patients with high amount. NSCLC patients show an altered N-glycan profile of plasma proteins that may be regarded as a supportive tool for cancer diagnosis.

Keywords: Glycomics, N-glycan, non-small cell lung carcinoma, plasma, diagnosis

DOI: 10.3233/CBM-2012-0239

Journal: Cancer Biomarkers, vol. 10, no. 3-4, pp. 145-154, 2012