Evidence map›Paper›PMID 24977712›Full record

ArticlePloS one2014

The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer.

Charles J d'Adhemar, Cathy D Spillane, Michael F Gallagher, Mark Bates, Katie M Costello, Jacqui Barry-O'Crowley, Kathryn Haley, Niamh Kernan, Ciara Murphy, Paul C Smyth and 17 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

38 citing papers in PubMed, 53 citations in OpenAlex.

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4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

27 authors at 6 institutions in 2 countries.

Charles J d'AdhemarDepartment of Histopathology, Trinity College Dublin, Dublin, Ireland.
Cathy D SpillaneDepartment of Histopathology, Trinity College Dublin, Dublin, Ireland.
Michael F GallagherDepartment of Histopathology, Trinity College Dublin, Dublin, Ireland.
Mark BatesDepartment of Histopathology, Trinity College Dublin, Dublin, Ireland.
Katie M CostelloDepartment of Pathology, Coombe Women's & Infants University Hospital, Dublin, Ireland.
Jacqui Barry-O'CrowleyDepartment of Pathology, Coombe Women's & Infants University Hospital, Dublin, Ireland.
Kathryn HaleyDepartment of Obstetrics and Gynaecology, Trinity College Dublin, Dublin, Ireland.
Niamh KernanDepartment of Pathology, Coombe Women's & Infants University Hospital, Dublin, Ireland.
Ciara MurphyDepartment of Pathology, Coombe Women's & Infants University Hospital, Dublin, Ireland.
Paul C SmythDepartment of Histopathology, Trinity College Dublin, Dublin, Ireland.
Ken O'ByrneTranslational Research Institute, Princess Alexandra Hospital, Brisbane, Australia.
Stephen PenningtonCollege of Health Sciences, University College Dublin, Belfield, Dublin, Ireland.
Aoife A CookeDepartment of Histopathology, Trinity College Dublin, Dublin, Ireland.
Brendan FfrenchDepartment of Histopathology, Trinity College Dublin, Dublin, Ireland.
Cara M MartinDepartment of Histopathology, Trinity College Dublin, Dublin, Ireland.
Dearbhaile O'DonnellDepartment of Medical Oncology, St. James's Hospital, Dublin, Ireland.
Bryan HennessyDepartment of Medical Oncology, Royal College of Surgeons, Dublin, Ireland.
Britta StordalDepartment of Histopathology, Trinity College Dublin, Dublin, Ireland.
Stephen FinnDepartment of Histopathology, Trinity College Dublin, Dublin, Ireland.
Amanda McCannCollege of Health Sciences, University College Dublin, Belfield, Dublin, Ireland.
Noreen GleesonDepartment of Obstetrics and Gynaecology, Trinity College Dublin, Dublin, Ireland.
Tom D'ArcyDepartment of Obstetrics and Gynaecology, Trinity College Dublin, Dublin, Ireland.
Brian FloodDepartment of Histopathology, Trinity College Dublin, Dublin, Ireland.
Luke A J O'NeillDepartment of Biochemistry, Trinity College Dublin, Ireland.
Orla SheilsDepartment of Histopathology, Trinity College Dublin, Dublin, Ireland.
Sharon O'TooleDepartment of Histopathology, Trinity College Dublin, Dublin, Ireland; Department of Obstetrics and Gynaecology, Trinity College Dublin, Dublin, Ireland.
John J O'LearyDepartment of Histopathology, Trinity College Dublin, Dublin, Ireland; Department of Pathology, Coombe Women's & Infants University Hospital, Dublin, Ireland.
Trinity College Dublin · IECoombe Women & Infants University Hospital · IEUniversity College Dublin · IEPrincess Alexandra Hospital · AURoyal College of Surgeons in Ireland · IESt. James's Hospital · IE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The prognosis of epithelial ovarian cancer is poor in part due to the high frequency of chemoresistance. Recent evidence points to the Toll-like receptor-4 (TLR4), and particularly its adaptor protein MyD88, as one potential mediator of this resistance. This study aims to provide further evidence that MyD88 positive cancer cells are clinically significant, stem-like and reproducibly detectable for the purposes of prognostic stratification. Expression of TLR4 and MyD88 was assessed immunohistochemically in 198 paraffin-embedded ovarian tissues and in an embryonal carcinoma model of cancer stemness. In parallel, expression of TLR4 and MyD88 mRNA and regulatory microRNAs (miR-21 and miR-146a) was assessed, as well as in a series of chemosensitive and resistant cancer cells lines. Functional analysis of the pathway was assessed in chemoresistant SKOV-3 ovarian cancer cells. TLR4 and MyD88 expression can be reproducibly assessed via immunohistochemistry using a semi-quantitative scoring system. TLR4 expression was present in all ovarian epithelium (normal and neoplastic), whereas MyD88 was restricted to neoplastic cells, independent of tumour grade and associated with reduced progression-free and overall survival, in an immunohistological specific subset of serous carcinomas, p<0.05. MiR-21 and miR-146a expression was significantly increased in MyD88 negative cancers (p<0.05), indicating their participation in regulation. Significant alterations in MyD88 mRNA expression were observed between chemosensitive and chemoresistant cells and tissue. Knockdown of TLR4 in SKOV-3 ovarian cells recovered chemosensitivity. Knockdown of MyD88 alone did not. MyD88 expression was down-regulated in differentiated embryonal carcinoma (NTera2) cells, supporting the MyD88+ cancer stem cell hypothesis. Our findings demonstrate that expression of MyD88 is associated with significantly reduced patient survival and altered microRNA levels and suggest an intact/functioning TLR4/MyD88 pathway is required for acquisition of the chemoresistant phenotype. Ex vivo manipulation of ovarian cancer stem cell (CSC) differentiation can decrease MyD88 expression, providing a potentially valuable CSC model for ovarian cancer.

Indexed as

Gene Expression Regulation, NeoplasticAgedAntineoplastic Agents, PhytogenicCarcinoma, Ovarian EpithelialCell Line, TumorCystadenocarcinoma, SerousDrug Resistance, NeoplasmFemaleGenotypeHumansImmunohistochemistryMicroRNAsMiddle AgedMyeloid Differentiation Factor 88Neoplasms, Glandular and EpithelialNeoplastic Stem CellsAntineoplastic Agents, PhytogenicMicroRNAsMIRN146 microRNA, humanMIRN21 microRNA, humanMYD88 protein, humanMyeloid Differentiation Factor 88PaclitaxelRNA, Small InterferingTLR4 protein, humanToll-Like Receptor 4

Identifiers

PMID24977712
PMCPMC4076208
OpenAlexW2030678455

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.