Laboruntersuchungen zum Nachweis pathologischer Veränderungen der Glycosylierung von Glycoproteinen und -lipiden haben dank neuer analytischer Methoden zunehmende diagnostische Bedeutung. Das Symposium gibt einen Überblick über wichtige neue Glycosylierungsbiomarker mit Schwerpunkt Autoimmunerkrankungen, Onkologie und Seltene Krankheiten.
08:30 Uhr
V-10:
Congenital Disorders of Glycosylation (CDG)
Priv.-Doz Christian Thiel | Universitätsklinikum Heidelberg | Germany
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Priv.-Doz Christian Thiel | Universitätsklinikum Heidelberg | Germany
Glycosylation is one of the most common modifications of proteins and lipids. The glycan moieties are important for biochemical processes such as correct folding, solubility, directed transport, activity or protection against degradation and also mediate cell-matrix and cell-cell interactions. Due to the importance of the glycans for the organism, it is not surprising that patients with deficiency in one of the glycosylation pathways usually suffer from severe clinical signs. Common symptoms comprise e.g. psychomotor and mental retardation, cerebellar hypoplasia, ataxia, seizures and muscular hypotonia as well as coagulopathy, liver and heart failure. Meanwhile the disease group `Congenital Disorders of Glycosylation´ (CDG) summarizes more than 140 different monogenetic defects within the synthesis and transfer of N-, O- and C-glycans to glycoproteins and glycolipids. As some of the CDG defects are treatable by the simple oral supplementation of sugars, a rapid diagnostic investigation by biochemical verification of the hypoglycosylation status of serum marker proteins like transferrin or Apolipoprotein CIII via HPLC, IEF or mass spectrometry coupled with genetic analysis is essential for providing patients and their families with a reliable report. In particular, the analysis of glycans by mass spectrometry proves to be an ideal tool to monitor a patient's course of therapy. To provide an overview, we here will focus on the diagnostic procedure of CDG deficiencies and on the therapeutic outcome of selected CDG cases.
09:06 Uhr
V-11:
Altered glycosylation in cancer – diagnostic and therapeutic applications
Prof. Dr. Celso Reis | University of Porto | Portugal
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Autor:in:
Prof. Dr. Celso Reis | University of Porto | Portugal
1. i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal;
2. Ipatimup – Institute of Molecular Pathology and Immunology of the University of Porto, Portugal;
3. ICBAS - Institute of Biomedical Sciences Abel Salazar of the University of Porto, Portugal;
4. FMUP - Faculty of Medicine of the University of Porto, Portugal;
Alterations of glycosylation are common on the cell surface during the carcinogenesis process and are associated with cancer progression and poor prognosis of the patients [1]. Gastric cancer is a heterogeneous disease that requires multidisciplinary treatment. Current targeted therapy depend on patient stratification based on molecular features of the tumor [2]. This study reports the glycomic and glycoproteomic analyses in human gastric cancer cells. Our results show that alterations of glycosylation impact the activation of tyrosine kinase receptors, such as MET (HGFR, Hepatocyte growth factor receptor) and RON (MSPR, Macrophage-stimulating protein receptor), and human epidermal growth factor receptor 2 (ErbB2) in gastric cancer cells [3,4]. We also report on the expression of truncated simple glycan antigens, as associated with molecular subtypes of tumors, such as those displaying microsatellite instability [5]. These results supports novel functional aspects of glycosylation modifications occurring in key proteins in cancer and their potential as cancer biomarkers for patient stratification and therapeutic intervention [6].
[1] Pinho SS, Reis CA. Nature Rev. Cancer 2015, 15, 540-555.
[2] Cristescu, R. et al. Nat. Med. 2015, 21, 449–456.
[3] Mereiter S, et al. Biochim. Biophys. Acta 2016, 1860, 1795-1808.
[4] Duarte, HO. et al. Int J Mol Sci. 2017, 18(11).
[5] Mereiter S, et al. J Clin Med. 2018 Sep 5;7(9).
[6] Mereiter S, et al. Cancer Cell. 2019 Jul 8;36(1):6-16.