Evidence map›Paper›PMID 32555399›Full record

ArticleScientific reports2020

Combination of variations in inflammation- and endoplasmic reticulum-associated genes as putative biomarker for bevacizumab response in KRAS wild-type colorectal cancer.

Ana Barat, Dominiek Smeets, Bruce Moran, Wu Zhang, Shu Cao, Sudipto Das, Rut Klinger, Johannes Betge, Verena Murphy, Orna Bacon and 20 more

Abstract readValidation Study
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Trial
  2. Article
  3. Review
  4. Review
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

30 authors.

Ana BaratCentre for Systems Medicine and Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland. anabarat27@gmail.com.
Dominiek SmeetsVIB Vesalius Research Center, KU Leuven, Leuven, Belgium.
Bruce MoranUCD Conway Institute, University College Dublin, Dublin, Ireland.ORCID http://orcid.org/0000-0002-7266-0265
Wu ZhangUSC Norris Comprehensive Cancer Center, Los Angeles, USA.
Shu CaoUSC Norris Comprehensive Cancer Center, Los Angeles, USA.
Sudipto DasMolecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
Rut KlingerUCD, School of Biomolecular and Biomedical Science, Dublin, Ireland.
Johannes BetgeDepartment of Medicine II, University Hospital Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.ORCID http://orcid.org/0000-0001-9549-1866
Verena MurphyCancer Trials Ireland, Dublin, Ireland.ORCID http://orcid.org/0000-0003-3113-7854
Orna BaconCentre for Systems Medicine and Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland.
Elaine W KayDepartment of Pathology, Beaumont Hospital, Dublin, Ireland.
Nicole C T Van GriekenDepartment of Pathology, VU University Medical Center, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0001-9992-0760
Henk M W VerheulDepartment of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
Timo GaiserInstitute of Pathology, University Hospital Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Nadine SchulteDepartment of Medicine II, University Hospital Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Matthias P EbertDepartment of Medicine II, University Hospital Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Bozena FenderOncoMark Ltd., NovaUCD, Belfield Innovation Park, Dublin, Ireland.
Bryan T HennessyDepartment of Medical Oncology, Beaumont Hospital, Dublin, Ireland.
Deborah A McNamaraDepartment of Surgery, Beaumont Hospital, Dublin, Ireland.
Darran O'ConnorMolecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
William M GallagherUCD Conway Institute, University College Dublin, Dublin, Ireland.
Chiara CremoliniUnit of Medical Oncology 2, Department of Translational Research and New Technologies in Medicine and Surgery, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy.
Fotios LoupakisOncology Unit, Istituto Oncologico Veneto, IOV-IRCCS, Padua, Italy.
Aparna ParikhDivision of Hematology and Oncology, Massachusetts General Hospital, Boston, USA.
Christoph MancaoOncology Biomarker Development, Genentech Inc., San Francisco, USA.
Bauke YlstraDepartment of Pathology, VU University Medical Center, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0001-9479-3010
Diether LambrechtsVIB Vesalius Research Center, KU Leuven, Leuven, Belgium.
Heinz-Josef LenzUSC Norris Comprehensive Cancer Center, Los Angeles, USA.ORCID http://orcid.org/0000-0003-2178-9568
Annette T ByrneCentre for Systems Medicine and Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland.
Jochen H M PrehnCentre for Systems Medicine and Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland. jprehn@rcsi.ie.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chemotherapy combined with the angiogenesis inhibitor bevacizumab (BVZ) is approved as a first-line treatment in metastatic colorectal cancer (mCRC). Limited clinical benefit underpins the need for improved understanding of resistance mechanisms and the elucidation of novel predictive biomarkers. We assessed germline single-nucleotide polymorphisms (SNPs) in 180 mCRC patients (Angiopredict [APD] cohort) treated with combined BVZ + chemotherapy and investigated previously reported predictive SNPs. We further employed a machine learning approach to identify novel associations. In the APD cohort IL8 rs4073 any A carriers, compared to TT carriers, were associated with worse progression-free survival (PFS) (HR = 1.51, 95% CI:1.03-2.22, p-value = 0.037) and TBK1 rs7486100 TT carriers, compared to any A carriers, were associated with worse PFS in KRAS wild-type (wt) patients (HR = 1.94, 95% CI:1.04-3.61, p-value = 0.037), replicating previous findings. Machine learning identified novel associations in genes encoding the inflammasome protein NLRP1 and the ER protein Sarcalumenin (SRL). A negative association between PFS and carriers of any A at NLRP1 rs12150220 and AA for SRL rs13334970 in APD KRAS wild-type patients (HR = 4.44, 95% CI:1.23-16.13, p-value = 0.005), which validated in two independent clinical cohorts involving BVZ, MAVERICC and TRIBE. Our findings highlight a key role for inflammation and ER signalling underpinning BVZ + chemotherapy responsiveness.

Indexed as

Adaptor Proteins, Signal TransducingAgedAngiogenesis InhibitorsApoptosis Regulatory ProteinsBevacizumabBiomarkers, TumorCohort StudiesColorectal NeoplasmsCombined Modality TherapyEndoplasmic ReticulumFemaleGenetic Association StudiesHumansInflammationMachine LearningMaleAdaptor Proteins, Signal TransducingAngiogenesis InhibitorsApoptosis Regulatory ProteinsBevacizumabBiomarkers, TumorKRAS protein, humanMembrane ProteinsNLRP1 protein, humanNLR ProteinsProto-Oncogene Proteins p21(ras)sarcalumenin

Identifiers

PMID32555399
PMCPMC7299973

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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.