Evidence map›Paper›PMID 26497652›Full record

ArticleGenome medicine2015

HOTAIR and its surrogate DNA methylation signature indicate carboplatin resistance in ovarian cancer.

Andrew E Teschendorff, Shih-Han Lee, Allison Jones, Heidi Fiegl, Marie Kalwa, Wolfgang Wagner, Kantaraja Chindera, Iona Evans, Louis Dubeau, Arturo Orjalo and 19 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genome medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed, 3 pooled it
6.7field-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

94 citing papers in PubMed, 3 syntheses or guidelines pooled it, 153 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Epigenetic networks coordinate DNA methylation across the genome.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
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34 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

29 authors at 18 institutions in 10 countries.

Andrew E TeschendorffStatistical Genomics Group, UCL Cancer Institute, University College London, London, UK. a.teschendorff@ucl.ac.uk.
Shih-Han LeeDepartment of Women's Cancer, UCL Elizabeth Garrett Anderson Institute for Women's Health, University College London, London, UK. lees7@mskcc.org.
Allison JonesDepartment of Women's Cancer, UCL Elizabeth Garrett Anderson Institute for Women's Health, University College London, London, UK. allison.jones@ucl.ac.uk.
Heidi FieglDepartment of Gynaecology and Obstetrics, Innsbruck Medical University, Innsbruck, Austria. heidelinde.fiegl@i-med.ac.at.
Marie KalwaHelmholtz-Institute for Biomedical Technology, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Aachen, Germany. marie.kalwa@rwth-aachen.de.
Wolfgang WagnerHelmholtz-Institute for Biomedical Technology, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Aachen, Germany. wwagner@ukaachen.de.
Kantaraja ChinderaDepartment of Women's Cancer, UCL Elizabeth Garrett Anderson Institute for Women's Health, University College London, London, UK. k.chindera@ucl.ac.uk.
Iona EvansDepartment of Women's Cancer, UCL Elizabeth Garrett Anderson Institute for Women's Health, University College London, London, UK. iona.evans@ucl.ac.uk.
Louis DubeauDepartment of Pathology, USC/Norris Comprehensive Cancer Center, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA. ldubeau@usc.edu.
Arturo OrjaloBiosearch Technologies, Novato, CA, USA. aorjalo@gmail.com.
Hugo M HorlingsDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada. hhorlings@bccrc.ca.
Lukas NiederreiterDepartment of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK. niederreiter.lukas@gmail.com.
Arthur KaserDepartment of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK. ak729@cam.ac.uk.
Winnie YangDepartment of Molecular Oncology, British Columbia Cancer Agency Research Centre, Vancouver, Canada. WYang@bccancer.bc.ca.
Ellen L GoodeDepartment of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA. egoode@mayo.edu.
Brooke L FridleyBiostatistics and Informatics Shared Resource, The University of Kansas Cancer Center, University of Kansas Medical Center, Kansas City, KS, USA. bfridley@kumc.edu.
Richard G JennerUCL Division of Infection and Immunity, University College London, London, UK. r.jenner@ucl.ac.uk.
Els M J J BernsDepartment of Medical Oncology, Erasmus MC-Cancer Center, Rotterdam, The Netherlands. p.berns@erasmusmc.nl.
Elisabeth WikCentre for Cancer Biomarkers, CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway. Elisabeth.Wik@k1.uib.no.
Helga B SalvesenDepartment of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway. helga.salvesen@k2.uib.no.
G Bea A WismanDepartment of Gynaecological Oncology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands. g.b.a.wisman@umcg.nl.
Ate G J van der ZeeDepartment of Gynaecological Oncology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands. a.g.j.van.der.zee@umcg.nl.
Ben DavidsonDivision of Pathology, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway. ben.davidson@ous-hf.no.
Claes G TropeDepartment of Gynaecological Oncology, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway. ctr@ous-hf.no.
Sandrina LambrechtsDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology and Leuven Cancer Institute, University Hospitals Leuven, Katholieke Universiteit Leuven, Leuven, Belgium. sandrina.lambrechts@uzleuven.be.
Ignace VergoteDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology and Leuven Cancer Institute, University Hospitals Leuven, Katholieke Universiteit Leuven, Leuven, Belgium. ignace.vergote@uzleuven.be.
Hilary CalvertDrug Development Group, UCL Cancer Institute, University College London, London, UK. hilary.calvert@ucl.ac.uk.
Ian J JacobsDepartment of Women's Cancer, UCL Elizabeth Garrett Anderson Institute for Women's Health, University College London, London, UK. i.jacobs@unsw.edu.au.
Martin WidschwendterDepartment of Women's Cancer, UCL Elizabeth Garrett Anderson Institute for Women's Health, University College London, London, UK. m.widschwendter@ucl.ac.uk.
University College London · GBHaukeland University Hospital · NOKU Leuven · BEOslo University Hospital · NORWTH Aachen University · DEUniversity College Hospital · GBUniversity of Cambridge · GBBC Cancer Agency · CABiosearch Technologies (United States) · USErasmus MC Cancer Institute · NLGenomics England · GBInnsbruck Medical University · ATMayo Clinic · USSouthern California University for Professional Studies · USUniversity Medical Center Groningen · NLUniversity of British Columbia · CAUniversity of Groningen · NLUniversity of Kansas · US

Funding

Role of the Mullerian Tract in Ovarian Cancer DevelopmentR01CA133117 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI DUBEAU, LOUIS · 2009 to 2013
$1.7M
NCI NIH HHS R01 CA133117NCI NIH HHS R01CA 133117
6 · The paper itself

Abstract

backgroundUnderstanding carboplatin resistance in ovarian cancer is critical for the improvement of patients' lives. Multipotent mesenchymal stem cells or an aggravated epithelial to mesenchymal transition phenotype of a cancer are integrally involved in pathways conferring chemo-resistance. Long non-coding RNA HOTAIR (HOX transcript antisense intergenic RNA) is involved in mesenchymal stem cell fate and cancer biology.

methodsWe analyzed HOTAIR expression and associated surrogate DNA methylation (DNAme) in 134 primary ovarian cancer cases (63 received carboplatin, 55 received cisplatin and 16 no chemotherapy). We validated our findings by HOTAIR expression and DNAme analysis in a multicentre setting of five additional sets, encompassing 946 ovarian cancers. Chemo-sensitivity has been assessed in cell culture experiments.

resultsHOTAIR expression was significantly associated with poor survival in carboplatin-treated patients with adjusted hazard ratios for death of 3.64 (95 % confidence interval [CI] 1.78-7.42; P < 0.001) in the discovery and 1.63 (95 % CI 1.04-2.56; P = 0.032) in the validation set. This effect was not seen in patients who did not receive carboplatin (0.97 [95 % CI 0.52-1.80; P = 0.932]). HOTAIR expression or its surrogate DNAme signature predicted poor outcome in all additional sets of carboplatin-treated ovarian cancer patients while HOTAIR expressors responded preferentially to cisplatin (multivariate interaction P = 0.008).

conclusionsNon-coding RNA HOTAIR or its more stable DNAme surrogate may indicate the presence of a subset of cells which confer resistance to carboplatin and can serve as (1) a marker to personalise treatment and (2) a novel target to overcome carboplatin resistance.

Indexed as

DNA MethylationAdultAgedAged, 80 and overAntineoplastic AgentsCarboplatinCell Line, TumorDrug Resistance, NeoplasmFemaleHumansMiddle AgedOvarian NeoplasmsRNA, Long NoncodingYoung AdultAntineoplastic AgentsCarboplatinHOTAIR long untranslated RNA, humanRNA, Long Noncoding

Identifiers

PMID26497652
PMCPMC4619324
OpenAlexW2129447411

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