Evidence map›Paper›PMID 26607327›Full record

ArticleBreast cancer research : BCR2015

The sialyl-glycolipid stage-specific embryonic antigen 4 marks a subpopulation of chemotherapy-resistant breast cancer cells with mesenchymal features.

Andrea Aloia, Evgeniya Petrova, Stefan Tomiuk, Ute Bissels, Olivier Déas, Massimo Saini, Franziska Maria Zickgraf, Steve Wagner, Saskia Spaich, Marc Sütterlin and 15 more

Open access · goldAbstract read
In one paragraph

Article in Breast cancer research : BCR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
2.2field-weighted citation impact, top 11% 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

41 citing papers in PubMed, 82 citations in OpenAlex.

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  9. Increased expression of SSEA-4 on TKI-resistant non-small cell lung cancer with EGFR-T790M mutation.Proceedings of the National Academy of Sciences of the United States of America · 2024
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  20. American journal of cancer research · 2022
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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

25 authors at 8 institutions in 3 countries.

Andrea AloiaMiltenyi Biotec GmbH, Friedrich-Ebert-Strasse 68, 51429, Bergisch Gladbach, Germany. aloia.andrea@libero.it.
Evgeniya PetrovaXenTech SAS, 4 rue Pierre Fontaine, 91000, Evry, France. epetrova@pasteur.fr.
Stefan TomiukMiltenyi Biotec GmbH, Friedrich-Ebert-Strasse 68, 51429, Bergisch Gladbach, Germany. stefant@miltenyibiotec.de.
Ute BisselsMiltenyi Biotec GmbH, Friedrich-Ebert-Strasse 68, 51429, Bergisch Gladbach, Germany. ute@miltenyibiotec.de.
Olivier DéasXenTech SAS, 4 rue Pierre Fontaine, 91000, Evry, France. olivier.deas@xentech.eu.
Massimo SainiHeidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) gGmbH, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. massimo.saini@hi-stem.de.
Franziska Maria ZickgrafHeidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) gGmbH, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. f.zickgraf@dkfz-heidelberg.de.
Steve WagnerHeidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) gGmbH, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. steve.wagner@icr.ac.uk.
Saskia SpaichFrauenklinik, University Medical Centre Mannheim, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany. saskia.spaich@umm.de.
Marc SütterlinFrauenklinik, University Medical Centre Mannheim, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany. marc.suetterlin@umm.de.
Andreas SchneeweissNational Center for Tumor Diseases, University Hospital Heidelberg, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany. andreas.schneeweiss@nct-heidelberg.de.
Manuel ReitbergerHeidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) gGmbH, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. m.reitberger@dkfz-heidelberg.de.
Silvia RübergMiltenyi Biotec GmbH, Friedrich-Ebert-Strasse 68, 51429, Bergisch Gladbach, Germany. silvia@miltenyibiotec.de.
Bernhard GerstmayerMiltenyi Biotec GmbH, Friedrich-Ebert-Strasse 68, 51429, Bergisch Gladbach, Germany. bernhard@miltenyibiotec.de.
David AgorkuMiltenyi Biotec GmbH, Friedrich-Ebert-Strasse 68, 51429, Bergisch Gladbach, Germany. davida@miltenyibiotec.de.
Sebastian KnöbelMiltenyi Biotec GmbH, Friedrich-Ebert-Strasse 68, 51429, Bergisch Gladbach, Germany. sebastiank@miltenyibiotec.de.
Annalisa TerranegraSidra Medical and Research Center, PO Box 26999, Doha, Qatar. aterranegra@sidra.org.
Monica FalleniDepartment of Health Sciences, University of Milan, Via Festa del Perdono 7, 20122, Milan, Italy. monica.falleni@unimi.it.
Laura SoldatiDepartment of Health Sciences, University of Milan, Via Festa del Perdono 7, 20122, Milan, Italy. laura.soldati@unimi.it.
Martin Ronald SprickHeidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) gGmbH, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. martin.sprick@hi-stem.de.
Andreas TrumppHeidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) gGmbH, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. a.trumpp@dkfz-heidelberg.de.
Jean-Gabriel JuddeXenTech SAS, 4 rue Pierre Fontaine, 91000, Evry, France. jgjudde@xentech.eu.
Andreas BosioMiltenyi Biotec GmbH, Friedrich-Ebert-Strasse 68, 51429, Bergisch Gladbach, Germany. andreasbo@miltenyibiotec.de.
Stefano CairoXenTech SAS, 4 rue Pierre Fontaine, 91000, Evry, France. Stefano.Cairo@xentech.eu.
Olaf HardtMiltenyi Biotec GmbH, Friedrich-Ebert-Strasse 68, 51429, Bergisch Gladbach, Germany. olaf@miltenyibiotec.de.
Miltenyi Biotec (Germany) · DEHeidelberg Institute for Stem Cell Technology and Experimental Medicine · DEUniversity Medical Centre Mannheim · DEUniversity of Milan · ITHeidelberg University · DENational Center for Tumor Diseases · DESidra Medical and Research Center · QAUniversity of Ferrara · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionChemotherapy resistance resulting in incomplete pathologic response is associated with high risk of metastasis and early relapse in breast cancer. The aim of this study was to identify and evaluate biomarkers of treatment-resistant tumor cells.

methodsWe performed a cell surface marker screen in triple-negative breast cancer patient-derived xenograft models treated with standard care genotoxic chemotherapy. Global expression profiling was used to further characterize the identified treatment-resistant subpopulations.

resultsHigh expression of sialyl-glycolipid stage-specific embryonic antigen 4 (SSEA4) was found in residual tumor cells surviving chemotherapy and in samples from metastatic patients who relapsed after neoadjuvant chemotherapy. Gene and microRNA (miRNA) expression profiling linked SSEA4 positivity with a mesenchymal phenotype and a deregulation of drug resistance pathways. Functional assays demonstrated a direct link between epithelial-mesenchymal transition (EMT) and SSEA4 expression. Interestingly, SSEA4 expression, EMT, and drug resistance seemed to be regulated posttranscriptionally. Finally, high expression of CMP-N-acetylneuraminate-β-galactosamide-α-2,3-sialyltransferase 2 (ST3GAL2), the rate-limiting enzyme of SSEA4 synthesis, was found to be associated with poor clinical outcome in breast and ovarian cancer patients treated with chemotherapy.

conclusionsIn this study, we identified SSEA4 as highly expressed in a subpopulation of tumor cells resistant to multiple commonly used chemotherapy drugs, as well as ST3GAL2, the rate-limiting enzyme of SSEA4 synthesis, as a predictive marker of poor outcome for breast and ovarian cancer patients undergoing chemotherapy. Both biomarkers and additionally identified regulatory miRNAs may be used to further understand chemoresistance, to stratify patient groups in order to avoid ineffective and painful therapies, and to develop alternative treatment regimens for breast cancer patients.

Indexed as

Drug Resistance, NeoplasmAnimalsBiomarkers, TumorBreast NeoplasmsCell Line, TumorEpithelial-Mesenchymal TransitionFemaleHumansMiceNeoplasm TransplantationStage-Specific Embryonic AntigensBiomarkers, Tumorstage-specific embryonic antigen-4Stage-Specific Embryonic Antigens

Identifiers

PMID26607327
PMCPMC4660783
OpenAlexW2175646320

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Registered trials

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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.