Lucas D Breen1, Maja Pučić-Baković2, Frano Vučković2, Karli Reiding3, Irena Trbojević-Akmačić2, Martina Šrajer Gajdošik1, Madeleine I Cook4, Michael J Lopez5, Manfred Wuhrer6, L M Camara4, Uroš Andjelković7, Damian E Dupuy8, Djuro Josić9. 1. Proteomics Core, COBRE CCRD, Rhode Island Hospital, Providence, RI, USA. 2. Genos Ltd., Glycobiology Research Laboratory, Zagreb, Croatia. 3. Leiden University Medical Center, Center for Proteomics and Metabolomics, Leiden, The Netherlands. 4. Department of Diagnostic Imaging, Warren Alpert Medical School, Brown University, Providence, RI, USA. 5. Center for Statistical Sciences, Brown University, Providence, RI, USA. 6. Leiden University Medical Center, Center for Proteomics and Metabolomics, Leiden, The Netherlands; VU University Amsterdam, Division of BioAnalytical Chemistry, Amsterdam, The Netherlands. 7. Department of Biotechnology, University of Rijeka, Croatia. 8. Department of Diagnostic Imaging, Warren Alpert Medical School, Brown University, Providence, RI, USA. Electronic address: DDupuy@Lifespan.org. 9. Department of Biotechnology, University of Rijeka, Croatia; Department of Medicine, Warren Alpert Medical School, Brown University, Providence, RI, USA. Electronic address: Djuro_Josic@brown.edu.
Abstract
BACKGROUND: Image-guided tumor ablation is a technique whereby needle-like applicators are placed directly into solid tumors under guidance typically with computed tomography or ultrasound. Changes in IgG and IgM antibody glycosylation were studied during ablation-induced immune response to cancer, and the use of glycosylation as a biomarker for diagnosis, prognosis and disease treatment was examined. METHODS: Plasma from 27 tumor patients was collected immediately before, after and for 6 months following ablation. IgG and IgM antibodies were isolated by use high-throughput chromatography, and analyzed by hydrophilic liquid chromatography. Thorough identification of glycan structures in each chromatography peak was performed by nano-liquid chromatography electrospray ionization mass spectrometry. RESULTS: Although antibody glycosylation was found to vary with cancer type, discernable patterns of change based on the successful treatment of tumors by ablation were not identified. One patient with renal clear cell carcinoma and poor disease outcome had unexpectedly high amount of oligomannose IgG glycans during the whole period of monitoring. In contrast, IgM antibodies did not follow the same pattern. CONCLUSIONS: These findings suggest that glycosylation patterns are indicative of an immune system that is unable to prevent different types of cancer, rather than products of the immunostimulatory response to the ablation of tumor itself. Analyses of the outcome effect suggested that IgG glycosylation and IgM glycosylation are not associated with tumor ablation. GENERAL SIGNIFICANCE: Present work opens a new way for parallel determination of glycosylation changes of both IgG and IgM antibodies by use of high-throughput methods, and their future use as biomarkers for disease diagnosis and prognosis. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc.
BACKGROUND: Image-guided tumor ablation is a technique whereby needle-like applicators are placed directly into solid tumors under guidance typically with computed tomography or ultrasound. Changes in IgG and IgM antibody glycosylation were studied during ablation-induced immune response to cancer, and the use of glycosylation as a biomarker for diagnosis, prognosis and disease treatment was examined. METHODS: Plasma from 27 tumorpatients was collected immediately before, after and for 6 months following ablation. IgG and IgM antibodies were isolated by use high-throughput chromatography, and analyzed by hydrophilic liquid chromatography. Thorough identification of glycan structures in each chromatography peak was performed by nano-liquid chromatography electrospray ionization mass spectrometry. RESULTS: Although antibody glycosylation was found to vary with cancer type, discernable patterns of change based on the successful treatment of tumors by ablation were not identified. One patient with renal clear cell carcinoma and poor disease outcome had unexpectedly high amount of oligomannose IgGglycans during the whole period of monitoring. In contrast, IgM antibodies did not follow the same pattern. CONCLUSIONS: These findings suggest that glycosylation patterns are indicative of an immune system that is unable to prevent different types of cancer, rather than products of the immunostimulatory response to the ablation of tumor itself. Analyses of the outcome effect suggested that IgG glycosylation and IgM glycosylation are not associated with tumor ablation. GENERAL SIGNIFICANCE: Present work opens a new way for parallel determination of glycosylation changes of both IgG and IgM antibodies by use of high-throughput methods, and their future use as biomarkers for disease diagnosis and prognosis. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc.
Authors: Gerda C M Vreeker; Kiki M H Vangangelt; Marco R Bladergroen; Simone Nicolardi; Wilma E Mesker; Manfred Wuhrer; Yuri E M van der Burgt; Rob A E M Tollenaar Journal: Glycoconj J Date: 2021-04-20 Impact factor: 2.916