Evidence map›Paper›PMID 29739952›Full record

Trial reportScientific reports2018

Translational study identifies XPF and MUS81 as predictive biomarkers for oxaliplatin-based peri-operative chemotherapy in patients with esophageal adenocarcinoma.

T P MacGregor, R Carter, R S Gillies, J M Findlay, C Kartsonaki, F Castro-Giner, N Sahgal, L M Wang, R Chetty, N D Maynard and 6 more

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

Trial report in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

9 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Molecular mechanisms associated with chemoresistance in esophageal cancer.Cellular and molecular life sciences : CMLS · 2022
    Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
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 3 countries.

T P MacGregorNIHR Oxford Biomedical Research Centre, Department of Oncology, University of Oxford, Oxford, UK.
R CarterNIHR Oxford Biomedical Research Centre, Department of Oncology, University of Oxford, Oxford, UK.
R S GilliesNIHR Oxford Biomedical Research Centre, Department of Oncology, University of Oxford, Oxford, UK.
J M FindlayDepartment of Upper GI Surgery, Churchill Hospital, Oxford, UK.
C KartsonakiNIHR Oxford Biomedical Research Centre, Department of Oncology, University of Oxford, Oxford, UK.
F Castro-GinerWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.ORCID 0000-0001-6111-0754
N SahgalLudwig Institute for Cancer Research, University of Oxford, Nuffield Department of Medicine, Oxford, UK.
L M WangNIHR Oxford Biomedical Research Centre/Department of Cellular Pathology/Radcliffe Department of Medicine, Oxford University Hospitals and University of Oxford, Oxford, UK.
R ChettyLaboratory Medicine Programme, University Health Network, Toronto, Canada.
N D MaynardDepartment of Upper GI Surgery, Churchill Hospital, Oxford, UK.
J B CazierNIHR Oxford Biomedical Research Centre, Department of Oncology, University of Oxford, Oxford, UK.
F BuffaNIHR Oxford Biomedical Research Centre, Department of Oncology, University of Oxford, Oxford, UK.
P J McHughDepartment of Oncology, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
I TomlinsonWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.ORCID 0000-0003-3037-1470
M R MiddletonNIHR Oxford Biomedical Research Centre, Department of Oncology, University of Oxford, Oxford, UK.
R A SharmaNIHR Oxford Biomedical Research Centre, Department of Oncology, University of Oxford, Oxford, UK. ricky.sharma@oncology.ox.ac.uk.
University of Oxford · GBCentre for Human Genetics · GBChurchill Hospital · GBChangi General Hospital · SGUCL Biomedical Research Centre · GBUniversity Health Network · CA

Funding

Cancer Research UK 16459Cancer Research UK 23969Cancer Research UK 8971Medical Research Council G0900747Medical Research Council G0900747 91070Wellcome TrustWellcome Trust 075491/Z/0Wellcome Trust 090532/Z/09/Z
6 · The paper itself

Abstract

Oxaliplatin-based chemotherapy is used to treat patients with esophageal adenocarcinoma (EAC), but no biomarkers are currently available for patient selection. We performed a prospective, clinical trial to identify potential biomarkers associated with clinical outcomes. Tumor tissue was obtained from 38 patients with resectable EAC before and after 2 cycles of oxaliplatin-fluorouracil chemotherapy. Pre-treatment mRNA expression of 280 DNA repair (DNAR) genes was tested for association with histopathological regression at surgery, disease-free survival (DFS) and overall survival (OS). High expression of 13 DNA damage repair genes was associated with DFS less than one year (P < 0.05); expression of 11 DNAR genes were associated with worse OS (P < 0.05). From clinical associations with outcomes, two genes, ERCC1 and EME1, were identified as candidate biomarkers. In cell lines in vitro, we showed the mechanism of action related to repair of oxaliplatin-induced DNA damage by depletion and knockout of protein binding partners of the candidate biomarkers, XPF and MUS81 respectively. In clinical samples from the clinical trial, pre-treatment XPF protein levels were associated with pathological response, and MUS81 protein was associated with 1-year DFS. XPF and MUS81 merit further validation in prospective clinical trials as biomarkers that may predict clinical response of EAC to oxaliplatin-based chemotherapy.

Indexed as

AdenocarcinomaAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorDisease-Free SurvivalDNA-Binding ProteinsDNA DamageEndonucleasesEsophageal NeoplasmsFemaleFluorouracilHumansMaleMiddle AgedOxaliplatinProtein BiosynthesisBiomarkers, TumorDNA-Binding ProteinsEndonucleasesFluorouracilMUS81 protein, humanOxaliplatinxeroderma pigmentosum group F protein

Identifiers

PMID29739952
PMCPMC5940885
OpenAlexW2807466473

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.