Analysis of serum glycome by lectin microarrays for prostate cancer patients - a search for aberrant glycoforms
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ORIGINAL ARTICLE
Analysis of serum glycome by lectin microarrays for prostate cancer patients - a search for aberrant glycoforms Tomas Bertok 1,2 & Eduard Jane 1 & Nikola Chrenekova 1 & Stefania Hroncekova 1 & Aniko Bertokova 1 & Michal Hires 1 & Alica Vikartovska 1 & Petra Kubanikova 3 & Roman Sokol 3 & Juraj Fillo 4 & Peter Kasak 5 & Lubor Borsig 6,7 & Jan Tkac 1,2 Received: 27 March 2020 / Revised: 31 July 2020 / Accepted: 19 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract This is the first work focused on glycoprofiling of whole N- and O- glycome using lectins in an array format applied for analysis of serum samples from healthy individuals, benign prostate hyperplasia (BPH) patients, and prostate cancer (PCa) patients. Lectin microarray was prepared using traditional lectins with the incorporation of 2 recombinant bacterial lectins and 3 human lectins (17 lectins in total). Clinical validation of glycans as biomarkers was done in two studies: discrimination of healthy individuals with BPH patients vs. PCa patients (C vs. PCa) and discrimination of healthy individuals vs. BPH and PCa patients (H vs. PCond). Single lectins (17 lectins) and a combination of two lectins (136 binary lectin combinations) were applied in the clinical validation of glycan biomarkers providing 153 AUC values from ROC curves for both studies (C vs. PCa and H vs. PCond). Potential N- and O-glycans as biomarkers were identified and possible carriers of these glycans are shortly discussed. Keywords Serum . N- and O-glycome . Prostate cancer . Lectin microarrays . Diagnostics . Clinical validation
Introduction Prostate cancer (PCa) is a leading cause of deaths among men with an incidence of 1.1 million cases a year resulting in 366,000 deaths annually [1]. With ageing of the population, there is a projection that by 2035 there will be 2.1 million PCa cases with Supplementary Information The online version of this article (https:// doi.org/10.1007/s10719-020-09958-4) contains supplementary material, which is available to authorized users. * Jan Tkac [email protected] 1
Institute of Chemistry, Slovak Academy of Sciences, Dubravska cesta 9, Bratislava 845 38, Slovakia
2
Glycanostics, Ltd, Slovak Academy of Sciences, Dubravska cesta 9, Bratislava 845 38, Slovakia
3
Private Urological Ambulance, Piaristicka 6, 911 01 Trencin, Slovakia
4
University Hospital Bratislava, Mickiewiczova 13, 81107 Bratislava, Slovakia
5
Center for Advanced Materials, Qatar University, P.O. Box 2713, Doha, Qatar
6
Department of Physiology, University of Zurich, Zurich, Switzerland
7
Comprehensive Cancer Center, Zurich, Switzerland
up to 633,328 associated deaths [2]. The number of deaths can be significantly reduced only by accurate early stage PCa diagnostics. The main reason behind the anticipated increase of PCa incidence and associated deaths is the fact that the current PCa biomarker - the level of prostate specific antigen (PSA) in the blood is not reliable enough for accurate early stage PCa diagnostics
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