Evidence map›Paper›PMID 30700254›Full record

ArticleBMC cancer2019

Gene expression profiling of homologous recombination repair pathway indicates susceptibility for olaparib treatment in malignant pleural mesothelioma in vitro.

Sabrina Borchert, Michael Wessolly, Jan Schmeller, Elena Mairinger, Jens Kollmeier, Thomas Hager, Thomas Mairinger, Thomas Herold, Daniel C Christoph, Robert F H Walter and 6 more

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

Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
4.0field-weighted citation impact, top 6% 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

24 citing papers in PubMed, 38 citations in OpenAlex.

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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

16 authors at 6 institutions in 1 country.

Sabrina BorchertInstitute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. sabrina.borchert@uk-essen.de.ORCID http://orcid.org/0000-0002-0447-3206
Michael WessollyInstitute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Jan SchmellerInstitute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Elena MairingerInstitute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Jens KollmeierDepartment of Pneumology, Helios Klinikum Emil von Behring, Berlin, Germany.
Thomas HagerInstitute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Thomas MairingerDepartment of Pathology, Helios Klinikum Emil von Behring, Berlin, Germany.
Thomas HeroldInstitute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Daniel C ChristophDepartment of Medical Oncology, West German Cancer Centre, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Robert F H WalterInstitute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Wilfried E E EberhardtDepartment of Medical Oncology, West German Cancer Centre, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Till PlönesDepartment of Thoracic Surgery and Thoracic Endoscopy, Ruhrlandklinik, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Jeremias WohlschlaegerInstitute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Clemens AignerDepartment of Thoracic Surgery and Thoracic Endoscopy, Ruhrlandklinik, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Kurt Werner SchmidInstitute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Fabian D MairingerInstitute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
University of Duisburg-Essen · DERuhrlandklinik · DEHelios Klinikum Emil von Behring · DEDiakonissenkrankenhaus · DEEssen University Hospital · DEKliniken Essen-Mitte · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMalignant pleural mesothelioma (MPM) is a tumour arising from pleural cavities with poor prognosis. Multimodality treatment with pemetrexed combined with cisplatin shows unsatisfying response-rates of 40%. The reasons for the rather poor efficacy of chemotherapeutic treatment are largely unknown. However, it is conceivable that DNA repair mechanisms lead to an impaired therapy response. We hypothesize a major role of homologous recombination (HR) for genome stability and survival of this tumour. Therefore, we analysed genes compiled under the term "BRCAness". An inhibition of this pathway with olaparib might abrogate this effect and induce apoptosis.

methodsWe investigated the response of three MPM cell lines and lung fibroblasts serving as a control to treatment with pemetrexed, cisplatin and olaparib. Furthermore, we aimed to find possible correlations between response and gene expression patterns associated with BRCAness phenotype. Therefore, 91 clinical MPM samples were digitally screened for gene expression patterns of HR members.

resultsA BRCAness-dependent increase of apoptosis and senescence during olaparib-based treatment of BRCA-associated-protein 1 (BAP1)-mutated cell lines was observed. The gene expression pattern identified could be found in approx. 10% of patient samples. Against this background, patients could be grouped according to their defects in the HR system. Gene expression levels of Aurora Kinase A (AURKA), RAD50 as well as DNA damage-binding protein 2 (DDB2) could be identified as prognostic markers in MPM.

conclusionsDefects in HR compiled under the term BRCAness are a common event in MPM. The present data can lead to a better understanding of the underlaying cellular mechanisms and leave the door wide open for new therapeutic approaches for this severe disease with infaust prognosis. Response to Poly (ADP-ribose)-Polymerase (PARP)-Inhibition could be demonstrated in the BAP1-mutated NCI-H2452 cells, especially when combined with cisplatin. Thus, this combination therapy might be effective for up to 2/3 of patients, promising to enhance patients' clinical management and outcome.

Indexed as

Acid Anhydride HydrolasesAntineoplastic AgentsApoptosisAurora Kinase ABiomarkers, TumorCell Line, TumorCisplatinDNA-Binding ProteinsDNA Repair EnzymesGene Expression ProfilingGene Expression Regulation, NeoplasticHomologous RecombinationHumansLung NeoplasmsMesotheliomaMesothelioma, MalignantAcid Anhydride HydrolasesAntineoplastic AgentsAURKA protein, humanAurora Kinase ABiomarkers, TumorCisplatinDDB2 protein, humanDNA-Binding ProteinsDNA Repair EnzymesolaparibPemetrexedPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsRAD50 protein, humanBRCAness - BAP1Malignant pleural mesothelioma - overall survivalOlaparibPARP1

Identifiers

PMID30700254
PMCPMC6354412
OpenAlexW2941506207

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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.