Evidence map›Paper›PMID 34752419›Full record

ArticleJCI insight2021

Clinical importance of high-mannose, fucosylated, and complex N-glycans in breast cancer metastasis.

Klára Ščupáková, Oluwatobi T Adelaja, Benjamin Balluff, Vinay Ayyappan, Caitlin M Tressler, Nicole M Jenkinson, Britt Sr Claes, Andrew P Bowman, Ashley M Cimino-Mathews, Marissa J White and 3 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
6.2field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

62 citing papers in PubMed, 99 citations in OpenAlex.

  1. EML4-ALK fusion rewires transcriptomic, miRNA, and CAF-associated programs in non-small cell lung cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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  18. Altered Cell SurfaceJournal of proteome research · 2025
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2 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 2 countries.

Klára ŠčupákováMaastricht MultiModal Molecular Imaging Institute (M4I), Maastricht University, Maastricht, The Netherlands.
Oluwatobi T AdelajaThe Russell H. Morgan Department of Radiology and Radiological Science, Division of Cancer Imaging Research.
Benjamin BalluffMaastricht MultiModal Molecular Imaging Institute (M4I), Maastricht University, Maastricht, The Netherlands.
Vinay AyyappanThe Russell H. Morgan Department of Radiology and Radiological Science, Division of Cancer Imaging Research.
Caitlin M TresslerThe Russell H. Morgan Department of Radiology and Radiological Science, Division of Cancer Imaging Research.
Nicole M JenkinsonThe Russell H. Morgan Department of Radiology and Radiological Science, Division of Cancer Imaging Research.
Britt Sr ClaesMaastricht MultiModal Molecular Imaging Institute (M4I), Maastricht University, Maastricht, The Netherlands.
Andrew P BowmanMaastricht MultiModal Molecular Imaging Institute (M4I), Maastricht University, Maastricht, The Netherlands.
Ashley M Cimino-MathewsDepartment of Pathology.
Marissa J WhiteDepartment of Pathology.
Pedram ArganiDepartment of Pathology.
Ron Ma HeerenMaastricht MultiModal Molecular Imaging Institute (M4I), Maastricht University, Maastricht, The Netherlands.
Kristine GlundeThe Russell H. Morgan Department of Radiology and Radiological Science, Division of Cancer Imaging Research.
Maastricht University · NLCancer Research Center · USSidney Kimmel Comprehensive Cancer Center · USJohns Hopkins University · US

Funding

Medical Scientist Training ProgramT32GM136577 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI ANDREA L COX · 2020 to 2026
$13.4M
Opportunities for Pathology Trainees in Cancer ResearchT32CA193145 · NCI · JOHNS HOPKINS UNIVERSITY · PI ANDERS, ROBERT A., EBERHART, CHARLES G · 2015 to 2025
$2.6M
Hypoxia-derived molecular MSI signatures to predict breast cancer outcomeR01CA213492 · NCI · JOHNS HOPKINS UNIVERSITY · PI GLUNDE, KRISTINE, HEEREN, RON · 2017 to 2021
$2.1M
Molecular studies of the MR-detectable oncometabolite glycerophosphocholineR01CA213428 · NCI · JOHNS HOPKINS UNIVERSITY · PI GLUNDE, KRISTINE · 2017 to 2021
$1.9M
Reprogramming of creatine metabolism in breast cancer metastasisR01CA264901 · NCI · JOHNS HOPKINS UNIVERSITY · PI Kristine Glunde · 2022 to 2026
$1.8M
NCI NIH HHS R01 CA213428NCI NIH HHS R01 CA213492NCI NIH HHS R01 CA264901NCI NIH HHS T32 CA193145NIGMS NIH HHS T32 GM136577
6 · The paper itself

Abstract

backgroundAlthough aberrant glycosylation is recognized as a hallmark of cancer, glycosylation in clinical breast cancer (BC) metastasis has not yet been studied. While preclinical studies show that the glycocalyx coating of cancer cells is involved in adhesion, migration, and metastasis, glycosylation changes from primary tumor (PT) to various metastatic sites remain unknown in patients.

methodsWe investigated N-glycosylation profiles in 17 metastatic BC patients from our rapid autopsy program. Primary breast tumor, lymph node metastases, multiple systemic metastases, and various normal tissue cores from each patient were arranged on unique single-patient tissue microarrays (TMAs). We performed mass spectrometry imaging (MSI) combined with extensive pathology annotation of these TMAs, and this process enabled spatially differentiated cell-based analysis of N-glycosylation patterns in metastatic BC.

resultsN-glycan abundance increased during metastatic progression independently of BC subtype and treatment regimen, with high-mannose glycans most frequently elevated in BC metastases, followed by fucosylated and complex glycans. Bone metastasis, however, displayed increased core-fucosylation and decreased high-mannose glycans. Consistently, N-glycosylated proteins and N-glycan biosynthesis genes were differentially expressed during metastatic BC progression, with reduced expression of mannose-trimming enzymes and with elevated EpCAM, N-glycan branching, and sialyation enzymes in BC metastases versus PT.

conclusionWe show in patients that N-glycosylation of breast cancer cells undergoing metastasis occurs in a metastatic site-specific manner, supporting the clinical importance of high-mannose, fucosylated, and complex N-glycans as future diagnostic markers and therapeutic targets in metastatic BC.

fundingNIH grants R01CA213428, R01CA213492, R01CA264901, T32CA193145, Dutch Province Limburg "LINK", European Union ERA-NET TRANSCAN2-643638.

Indexed as

AdultAgedBreast NeoplasmsFemaleGlycosylationHumansMannoseMiddle AgedNeoplasm MetastasisPolysaccharidesMannosePolysaccharidesBreast cancerGlycobiologyMolecular pathologyOncology

Identifiers

PMID34752419
PMCPMC8783675
OpenAlexW3212526325

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.