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Glycosylation-Based Biomarkers in Diseases and Drug Delivery

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 18116

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Special Issue Editors

Dr. Julia Costa

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Guest Editor

Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal
Interests: protein glycosylation; biomarkers; glyco(proteo)mics; extracellular vesicles; glycosyltransferases; amyotrophic lateral sclerosis; cerebrospinal fluid; neurodegeneration; cancer

Prof. Dr. Salomé S. Pinho

E-Mail Website
Co-Guest Editor

Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal
Interests: Protein glycosylation; glycans; glycoproteomics; glycobiomarkers; glycoimmunology; oncobiology; Inflammation

Special Issue Information

Dear Colleagues,

Glycoconjugates, such as, glycoproteins, proteoglycans and glycolipids, are major components of cells and organisms. A high diversity of glycan structures are present in different cellular types, being involved in major cellular and molecular processes both in homeostasis and in diseases. Therefore, specific glycosignatures displayed by cells, tissues or biofluids constitute valuable biomarkers of disease with important clinical applications. In the field of cancer changes in glycosylation have long been recognized and, consequently, several glycan-based biomarkers have been identified. For other diseases, such as inflammation and neurological diseases, the potential of glycosylation as biomarker is also relevant.

Glycans mediate cell recognition events (e.g., by immune cells) through their interaction with lectins and receptors, which provide potential tools for drug delivery onto specific target cells, acting also as promising vaccines. In this context, glycosyltransferases and glycosidases, enzymes that participate in the biosynthesis of glycans in vivo, constitute useful tools for glycosylation remodeling.

This Special issue will include papers addressing glycoconjugates/glycosylation as relevant disease biomarkers that can aid in diagnosis and prognosis. The role of glycans in the understanding of disease ethiopathogenesis and as promising targets for new therapies in context of precision medicine are considered. Furthermore, studies on glycosylation for the improvement of targeted drug delivery are welcome.

Dr. Júlia Costa

Prof. Salomé S. Pinho

Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Glycan-based biomarkers for disease (particularly, cancer, neurodegeneration, chronic inflammatory diseases, neurological disorders, inflammation, autoimmunity, congenital disorders of glycosylation).
Glycans in the immune system.
Glyco(proteo)mics strategies for novel biomarker identification.
Glycosylation and metabolomics in disease.
Glycoconjugates/glycosylation from extracellular vesicles as biomarkers and implications in delivery.
Glycoengineering of nanoparticle surfaces aiming at improved delivery.
Lectins and glycan receptors in recognition mechanisms and diagnosis.

Published Papers (5 papers)

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Research

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24 pages, 3320 KiB

Open AccessArticle

Target Score—A Proteomics Data Selection Tool Applied to Esophageal Cancer Identifies GLUT1-Sialyl Tn Glycoforms as Biomarkers of Cancer Aggressiveness

by Sofia Cotton, Dylan Ferreira, Janine Soares, Andreia Peixoto, Marta Relvas-Santos, Rita Azevedo, Paulina Piairo, Lorena Diéguez, Carlos Palmeira, Luís Lima, André M. N. Silva, Lúcio Lara Santos and José Alexandre Ferreira

Int. J. Mol. Sci. 2021, 22(4), 1664; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041664 - 7 Feb 2021

Cited by 12 | Viewed by 3624

Abstract

Esophageal cancer (EC) is a life-threatening disease, demanding the discovery of new biomarkers and molecular targets for precision oncology. Aberrantly glycosylated proteins hold tremendous potential towards this objective. In the current study, a series of esophageal squamous cell carcinomas (ESCC) and EC-derived circulating tumor cells (CTCs) were screened by immunoassays for the sialyl-Tn (STn) antigen, a glycan rarely expressed in healthy tissues and widely observed in aggressive gastrointestinal cancers. An ESCC cell model was glycoengineered to express STn and characterized in relation to cell proliferation and invasion in vitro. STn was found to be widely present in ESCC (70% of tumors) and in CTCs in 20% of patients, being associated with general recurrence and reduced survival. Furthermore, STn expression in ESCC cells increased invasion in vitro, while reducing cancer cells proliferation. In parallel, an ESCC mass spectrometry-based proteomics dataset, obtained from the PRIDE database, was comprehensively interrogated for abnormally glycosylated proteins. Data integration with the Target Score, an algorithm developed in-house, pinpointed the glucose transporter type 1 (GLUT1) as a biomarker of poor prognosis. GLUT1-STn glycoproteoforms were latter identified in tumor tissues in patients facing worst prognosis. Furthermore, healthy human tissues analysis suggested that STn glycosylation provided cancer specificity to GLUT1. In conclusion, STn is a biomarker of worst prognosis in EC and GLUT1-STn glycoforms may be used to increase its specificity on the stratification and targeting of aggressive ESCC forms. Full article

(This article belongs to the Special Issue Glycosylation-Based Biomarkers in Diseases and Drug Delivery)

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12 pages, 2798 KiB

Open AccessArticle

A Potential Serum N-glycan Biomarker for Hepatitis C Virus-Related Early-Stage Hepatocellular Carcinoma with Liver Cirrhosis

by Mikito Higashi, Takeshi Yoshimura, Noriyoshi Usui, Yuichiro Kano, Akihiro Deguchi, Kazuhiro Tanabe, Youichi Uchimura, Shigeki Kuriyama, Yasuyuki Suzuki, Tsutomu Masaki and Kazuhiro Ikenaka

Int. J. Mol. Sci. 2020, 21(23), 8913; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21238913 - 24 Nov 2020

Cited by 8 | Viewed by 2307

Abstract

Detection of early-stage hepatocellular carcinoma (HCC) is beneficial for prolonging patient survival. However, the serum markers currently used show limited ability to identify early-stage HCC. In this study, we explored human serum N-glycans as sensitive markers to diagnose HCC in patients with cirrhosis. Using a simplified fluorescence-labeled N-glycan preparation method, we examined non-sialylated and sialylated N-glycan profiles from 71 healthy controls and 111 patients with hepatitis and/or liver cirrhosis (LC) with or without HCC. We found that the level of serum N-glycan A2G1(6)FB, a biantennary N-glycan containing core fucose and bisecting GlcNAc residues, was significantly higher in hepatitis C virus (HCV)-infected cirrhotic patients with HCC than in those without HCC. In addition, A2G1(6)FB was detectable in HCV-infected patients with early-stage HCC and could be a more accurate marker than alpha-fetoprotein (AFP) or protein induced by vitamin K absence or antagonists-II (PIVKA-II). Moreover, there was no apparent correlation between the levels of A2G1(6)FB and those of AFP or PIVKA-II. Thus, simultaneous use of A2G1(6)FB and traditional biomarkers could improve the accuracy of HCC diagnosis in HCV-infected patients with LC, suggesting that A2G1(6)FB may be a reliable biomarker for early-stage HCC patients. Full article

(This article belongs to the Special Issue Glycosylation-Based Biomarkers in Diseases and Drug Delivery)

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13 pages, 1447 KiB

Open AccessArticle

N-Glycoproteins Have a Major Role in MGL Binding to Colorectal Cancer Cell Lines: Associations with Overall Proteome Diversity

by Martina Pirro, Yassene Mohammed, Sandra J. van Vliet, Yoann Rombouts, Agnese Sciacca, Arnoud H. de Ru, George M. C. Janssen, Rayman T. N. Tjokrodirijo, Manfred Wuhrer, Peter A. van Veelen and Paul J. Hensbergen

Int. J. Mol. Sci. 2020, 21(15), 5522; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21155522 - 1 Aug 2020

Cited by 9 | Viewed by 3270

Abstract

Colorectal cancer (CRC) is the second-leading cause of cancer death worldwide due in part to a high proportion of patients diagnosed at advanced stages of the disease. For this reason, many efforts have been made towards new approaches for early detection and prognosis. Cancer-associated aberrant glycosylation, especially the Tn and STn antigens, can be detected using the macrophage galactose-type C-type lectin (MGL/CLEC10A/CD301), which has been shown to be a promising tool for CRC prognosis. We had recently identified the major MGL-binding glycoproteins in two high-MGL-binding CRC cells lines, HCT116 and HT29. However, we failed to detect the presence of O-linked Tn and STn glycans on most CRC glycoproteins recognized by MGL. We therefore investigated here the impact of N-linked and O-linked glycans carried by these proteins for the binding to MGL. In addition, we performed quantitative proteomics to study the major differences in proteins involved in glycosylation in these cells. Our results showed that N-glycans have a significant, previously underestimated, importance in MGL binding to CRC cell lines. Finally, we highlighted both common and cell-specific processes associated with a high-MGL-binding phenotype, such as differential levels of enzymes involved in protein glycosylation, and a transcriptional factor (CDX-2) involved in their regulation. Full article

(This article belongs to the Special Issue Glycosylation-Based Biomarkers in Diseases and Drug Delivery)

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Review

Jump to: Research

16 pages, 2767 KiB

Open AccessReview

Cracking the Breast Cancer Glyco-Code through Glycan-Lectin Interactions: Targeting Immunosuppressive Macrophages

by Nuno Lopes, Viviana G. Correia, Angelina S. Palma and Catarina Brito

Int. J. Mol. Sci. 2021, 22(4), 1972; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041972 - 17 Feb 2021

Cited by 8 | Viewed by 4043

Abstract

The immune microenvironment of breast cancer (BC) is composed by high macrophage infiltrates, correlated with the most aggressive subtypes. Tumour-associated macrophages (TAM) within the BC microenvironment are key regulators of immune suppression and BC progression. Nevertheless, several key questions regarding TAM polarisation by BC are still not fully understood. Recently, the modulation of the immune microenvironment has been described via the recognition of abnormal glycosylation patterns at BC cell surface. These patterns rise as a resource to identify potential targets on TAM in the BC context, leading to the development of novel immunotherapies. Herein, we will summarize recent studies describing advances in identifying altered glycan structures in BC cells. We will focus on BC-specific glycosylation patterns known to modulate the phenotype and function of macrophages recruited to the tumour site, such as structures with sialylated or N-acetylgalactosamine epitopes. Moreover, the lectins present at the surface of macrophages reported to bind to such antigens, inducing tumour-prone TAM phenotypes, will also be highlighted. Finally, we will discuss and give our view on the potential and current challenges of targeting these glycan-lectin interactions to reshape the immunosuppressive landscape of BC. Full article

(This article belongs to the Special Issue Glycosylation-Based Biomarkers in Diseases and Drug Delivery)

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16 pages, 3499 KiB

Open AccessReview

C-Type Lectins in Veterinary Species: Recent Advancements and Applications

by Dimitri Leonid Lindenwald and Bernd Lepenies

Int. J. Mol. Sci. 2020, 21(14), 5122; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21145122 - 20 Jul 2020

Cited by 14 | Viewed by 4208

Abstract

C-type lectins (CTLs), a superfamily of glycan-binding receptors, play a pivotal role in the host defense against pathogens and the maintenance of immune homeostasis of higher animals and humans. CTLs in innate immunity serve as pattern recognition receptors and often bind to glycan structures in damage- and pathogen-associated molecular patterns. While CTLs are found throughout the whole animal kingdom, their ligand specificities and downstream signaling have mainly been studied in humans and in model organisms such as mice. In this review, recent advancements in CTL research in veterinary species as well as potential applications of CTL targeting in veterinary medicine are outlined. Full article

(This article belongs to the Special Issue Glycosylation-Based Biomarkers in Diseases and Drug Delivery)

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