Evidence map›Paper›PMID 25261936›Full record

ArticleMolecular cancer2014

Molecular profiling of circulating tumor cells links plasticity to the metastatic process in endometrial cancer.

Lorena Alonso-Alconada, Laura Muinelo-Romay, Kadri Madissoo, Antonio Diaz-Lopez, Camilla Krakstad, Jone Trovik, Elisabeth Wik, Dharani Hapangama, Lieve Coenegrachts, Amparo Cano and 22 more

Open access · goldAbstract read
In one paragraph

Article in Molecular cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
4.9field-weighted citation impact, top 3% 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

63 citing papers in PubMed, 100 citations in OpenAlex.

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  13. Endometrial Cancer Stem Cells: Where Do We Stand and Where Should We Go?International journal of molecular sciences · 2022
    Review
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3 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

32 authors at 19 institutions in 6 countries.

Lorena Alonso-Alconada
Laura Muinelo-Romay
Kadri Madissoo
Antonio Diaz-Lopez
Camilla Krakstad
Jone Trovik
Elisabeth Wik
Dharani Hapangama
Lieve Coenegrachts
Amparo Cano
Antonio Gil-Moreno
Luis Chiva
Juan Cueva
Maria Vieito
Eugenia Ortega
Javier Mariscal
Eva Colas
Josep Castellvi
Maite Cusido
Xavier Dolcet
Hans W Nijman
Tjalling Bosse
John A Green
Andrea Romano
Jaume Reventos
Rafael Lopez-Lopez
Helga B Salvesen
Frederic Amant
Xavier Matias-Guiu
Gema Moreno-Bueno
Miguel AbalTranslational Medical Oncology; Health Research Institute of Santiago (IDIS), SERGAS, Trav, Choupana s/n 15706, Santiago de Compostela, Spain. miguel.abal.posada@sergas.es.
ENITEC Consortium
Haukeland University Hospital · NOInstituto de Investigación Sanitaria de Santiago · ESServicio Gallego de Salud · ESUniversitat Autònoma de Barcelona · ESKU Leuven · BEUniversidad Autónoma de Madrid · ESUniversitat de Lleida · ESUniversity of Bergen · NOHospital Universitari Arnau de Vilanova · ESInstituto de Investigaciones Biomédicas Sols-Morreale · ESLeiden University Medical Center · NLLiverpool Women's Hospital · GBMaastricht University Medical Centre · NLMD Anderson Cancer Center Madrid · ESTranslational Research in Oncology · FRUniversity Medical Center Groningen · NLUniversity of Liverpool · GBUSP Institut Universitari Dexeus · ESVall d'Hebron Institut de Recerca · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAbout 20% of patients diagnosed with endometrial cancer (EC) are considered high-risk with unfavorable prognosis. In the framework of the European Network for Individualized Treatment in EC (ENITEC), we investigated the presence and phenotypic features of Circulating Tumor Cells (CTC) in high-risk EC patients.

methodsCTC isolation was carried out in peripheral blood samples from 34 patients, ranging from Grade 3 Stage IB to Stage IV carcinomas and recurrences, and 27 healthy controls using two methodologies. Samples were subjected to EpCAM-based immunoisolation using the CELLection™ Epithelial Enrich kit (Invitrogen, Dynal) followed by RTqPCR analysis. The phenotypic determinants of endometrial CTC in terms of pathogenesis, hormone receptor pathways, stem cell markers and epithelial to mesenchymal transition (EMT) drivers were asked. Kruskal-Wallis analysis followed by Dunn's post-test was used for comparisons between groups. Statistical significance was set at p < 0.05.

resultsEpCAM-based immunoisolation positively detected CTC in high-risk endometrial cancer patients. CTC characterization indicated a remarkable plasticity phenotype defined by the expression of the EMT markers ETV5, NOTCH1, SNAI1, TGFB1, ZEB1 and ZEB2. In addition, the expression of ALDH and CD44 pointed to an association with stemness, while the expression of CTNNB1, STS, GDF15, RELA, RUNX1, BRAF and PIK3CA suggested potential therapeutic targets. We further recapitulated the EMT phenotype found in endometrial CTC through the up-regulation of ETV5 in an EC cell line, and validated in an animal model of systemic dissemination the propensity of these CTC in the accomplishment of metastasis.

conclusionsOur results associate the presence of CTC with high-risk EC. Gene-expression profiling characterized a CTC-plasticity phenotype with stemness and EMT features. We finally recapitulated this CTC-phenotype by over-expressing ETV5 in the EC cell line Hec1A and demonstrated an advantage in the promotion of metastasis in an in vivo mouse model of CTC dissemination and homing.

Indexed as

Gene Expression ProfilingAgedAnimalsCell SeparationDisease Models, AnimalDNA-Binding ProteinsEndometrial NeoplasmsEpithelial-Mesenchymal TransitionFemaleGene Expression Regulation, NeoplasticHumansMice, NudeNeoplasm MetastasisNeoplastic Cells, CirculatingPhenotypeRisk FactorsDNA-Binding ProteinsETV5 protein, humanTranscription Factors

Identifiers

PMID25261936
PMCPMC4190574
OpenAlexW2097231959

What OpenQuestion holds

Textmetadata
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.