Levels of plasma glycan-binding auto-IgG biomarkers improve the accuracy of prostate cancer diagnosis
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Levels of plasma glycan‑binding auto‑IgG biomarkers improve the accuracy of prostate cancer diagnosis Julia Matzenbacher dos Santos1,2 · Aby Joiakim1 · David J. Kaplan1 · David A. Putt1 · German Perez Bakovic3 · Shannon L. Servoss3 · Benjamin A. Rybicki4 · Alan A. Dombkowski5 · Hyesook Kim1 Received: 3 March 2020 / Accepted: 7 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Strategies to improve the early diagnosis of prostate cancer will provide opportunities for earlier intervention. The bloodbased prostate-specific antigen (PSA) assay is widely used for prostate cancer diagnosis but specificity of the assay is not satisfactory. An algorithm based on serum levels of PSA combined with other serum biomarkers may significantly improve prostate cancer diagnosis. Plasma glycan-binding IgG/IgM studies suggested that glycan patterns differ between normal and tumor cells. We hypothesize that in prostate cancer glycoproteins or glycolipids are secreted from tumor tissues into the blood and induce auto-immunoglobulin (Ig) production. A 24-glycan microarray and a 5-glycan subarray were developed using plasma samples obtained from 35 prostate cancer patients and 54 healthy subjects to identify glycan-binding auto-IgGs. Neu5Acα2-8Neu5Acα2-8Neu5Acα (G81)-binding auto-IgG was higher in prostate cancer samples and, when levels of G81-binding auto-IgG and growth differentiation factor-15 (GDF-15 or NAG-1) were combined with levels of PSA, the prediction rate of prostate cancer increased from 78.2% to 86.2% than with PSA levels alone. The G81 glycanbinding auto-IgG fraction was isolated from plasma samples using G81 glycan-affinity chromatography and identified by N-terminal sequencing of the 50 kDa heavy chain variable region of the IgG. G81 glycan-binding 25 kDa fibroblast growth factor-1 (FGF1) fragment was also identified by N-terminal sequencing. Our results demonstrated that a multiplex diagnostic combining G81 glycan-binding auto-IgG, GDF-15/NAG-1 and PSA (≥ 2.1 ng PSA/ml for cancer) increased the specificity of prostate cancer diagnosis by 8%. The multiplex assessment could improve the early diagnosis of prostate cancer thereby allowing the prompt delivery of prostate cancer treatment. Keywords Prostate cancer · Glycan-binding auto-IgG · Biomarker · PSA · GDF-15/NAG-1
Introduction
* Hyesook Kim [email protected] 1
Detroit R&D, Inc., 2727 Second Ave. Suite 4113, Detroit, MI, USA
2
Department of Education, Health and Human Performance, Fairmont State University, Fairmont, WV, USA
3
Department of Chemical Engineering, University of Arkansas, Fayetteville, AR, USA
4
Henry Ford Health System, Detroit, MI, USA
5
Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, USA
Prostate cancer is one of the most common malignant tumors among the male population, causing cancer-related deaths [1]. Early diagnosis strategies could improve prostate cancer outcomes by providing care at the earliest possible stage. Serum biomarkers are widely us
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