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Glycosylation in Indolent, Significant and Aggressive Prostate Cancer by Automated High-Throughput N-Glycan Profiling

The diagnosis and treatment of prostate cancer (PCa) is a major health-care concern worldwide. This cancer can manifest itself in many distinct forms and the transition from clinically indolent PCa to the more invasive aggressive form remains poorly understood. It is now universally accepted that gl...

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Autores principales: Gilgunn, Sarah, Murphy, Keefe, Stöckmann, Henning, Conroy, Paul J., Murphy, T. Brendan, Watson, R. William, O’Kennedy, Richard J., Rudd, Pauline M., Saldova, Radka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730228/
https://www.ncbi.nlm.nih.gov/pubmed/33287410
http://dx.doi.org/10.3390/ijms21239233
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author Gilgunn, Sarah
Murphy, Keefe
Stöckmann, Henning
Conroy, Paul J.
Murphy, T. Brendan
Watson, R. William
O’Kennedy, Richard J.
Rudd, Pauline M.
Saldova, Radka
author_facet Gilgunn, Sarah
Murphy, Keefe
Stöckmann, Henning
Conroy, Paul J.
Murphy, T. Brendan
Watson, R. William
O’Kennedy, Richard J.
Rudd, Pauline M.
Saldova, Radka
author_sort Gilgunn, Sarah
collection PubMed
description The diagnosis and treatment of prostate cancer (PCa) is a major health-care concern worldwide. This cancer can manifest itself in many distinct forms and the transition from clinically indolent PCa to the more invasive aggressive form remains poorly understood. It is now universally accepted that glycan expression patterns change with the cellular modifications that accompany the onset of tumorigenesis. The aim of this study was to investigate if differential glycosylation patterns could distinguish between indolent, significant, and aggressive PCa. Whole serum N-glycan profiling was carried out on 117 prostate cancer patients’ serum using our automated, high-throughput analysis platform for glycan-profiling which utilizes ultra-performance liquid chromatography (UPLC) to obtain high resolution separation of N-linked glycans released from the serum glycoproteins. We observed increases in hybrid, oligomannose, and biantennary digalactosylated monosialylated glycans (M5A1G1S1, M8, and A2G2S1), bisecting glycans (A2B, A2(6)BG1) and monoantennary glycans (A1), and decreases in triantennary trigalactosylated trisialylated glycans with and without core fucose (A3G3S3 and FA3G3S3) with PCa progression from indolent through significant and aggressive disease. These changes give us an insight into the disease pathogenesis and identify potential biomarkers for monitoring the PCa progression, however these need further confirmation studies.
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spelling pubmed-77302282020-12-12 Glycosylation in Indolent, Significant and Aggressive Prostate Cancer by Automated High-Throughput N-Glycan Profiling Gilgunn, Sarah Murphy, Keefe Stöckmann, Henning Conroy, Paul J. Murphy, T. Brendan Watson, R. William O’Kennedy, Richard J. Rudd, Pauline M. Saldova, Radka Int J Mol Sci Article The diagnosis and treatment of prostate cancer (PCa) is a major health-care concern worldwide. This cancer can manifest itself in many distinct forms and the transition from clinically indolent PCa to the more invasive aggressive form remains poorly understood. It is now universally accepted that glycan expression patterns change with the cellular modifications that accompany the onset of tumorigenesis. The aim of this study was to investigate if differential glycosylation patterns could distinguish between indolent, significant, and aggressive PCa. Whole serum N-glycan profiling was carried out on 117 prostate cancer patients’ serum using our automated, high-throughput analysis platform for glycan-profiling which utilizes ultra-performance liquid chromatography (UPLC) to obtain high resolution separation of N-linked glycans released from the serum glycoproteins. We observed increases in hybrid, oligomannose, and biantennary digalactosylated monosialylated glycans (M5A1G1S1, M8, and A2G2S1), bisecting glycans (A2B, A2(6)BG1) and monoantennary glycans (A1), and decreases in triantennary trigalactosylated trisialylated glycans with and without core fucose (A3G3S3 and FA3G3S3) with PCa progression from indolent through significant and aggressive disease. These changes give us an insight into the disease pathogenesis and identify potential biomarkers for monitoring the PCa progression, however these need further confirmation studies. MDPI 2020-12-03 /pmc/articles/PMC7730228/ /pubmed/33287410 http://dx.doi.org/10.3390/ijms21239233 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gilgunn, Sarah
Murphy, Keefe
Stöckmann, Henning
Conroy, Paul J.
Murphy, T. Brendan
Watson, R. William
O’Kennedy, Richard J.
Rudd, Pauline M.
Saldova, Radka
Glycosylation in Indolent, Significant and Aggressive Prostate Cancer by Automated High-Throughput N-Glycan Profiling
title Glycosylation in Indolent, Significant and Aggressive Prostate Cancer by Automated High-Throughput N-Glycan Profiling
title_full Glycosylation in Indolent, Significant and Aggressive Prostate Cancer by Automated High-Throughput N-Glycan Profiling
title_fullStr Glycosylation in Indolent, Significant and Aggressive Prostate Cancer by Automated High-Throughput N-Glycan Profiling
title_full_unstemmed Glycosylation in Indolent, Significant and Aggressive Prostate Cancer by Automated High-Throughput N-Glycan Profiling
title_short Glycosylation in Indolent, Significant and Aggressive Prostate Cancer by Automated High-Throughput N-Glycan Profiling
title_sort glycosylation in indolent, significant and aggressive prostate cancer by automated high-throughput n-glycan profiling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730228/
https://www.ncbi.nlm.nih.gov/pubmed/33287410
http://dx.doi.org/10.3390/ijms21239233
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