Evidence map›Paper›PMID 30116025›Full record

ArticleBritish journal of cancer2018

Proteomic phenotyping of metastatic melanoma reveals putative signatures of MEK inhibitor response and prognosis.

Christoph Krisp, Robert Parker, Dana Pascovici, Nicholas K Hayward, James S Wilmott, John F Thompson, Graham J Mann, Georgina V Long, Richard A Scolyer, Mark P Molloy

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

Article in British journal of cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.5field-weighted citation impact, top 37% 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

6 citing papers in PubMed, 12 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

10 authors at 4 institutions in 2 countries.

Christoph KrispAustralian Proteome Analysis Facility (APAF), Department of Chemistry & Biomolecular Sciences, Macquarie University, Sydney, NSW, Australia.
Robert ParkerAustralian Proteome Analysis Facility (APAF), Department of Chemistry & Biomolecular Sciences, Macquarie University, Sydney, NSW, Australia.
Dana PascoviciAustralian Proteome Analysis Facility (APAF), Department of Chemistry & Biomolecular Sciences, Macquarie University, Sydney, NSW, Australia.
Nicholas K HaywardOncogenomics Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
James S WilmottMelanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
John F ThompsonMelanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
Graham J MannMelanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
Georgina V LongMelanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
Richard A ScolyerMelanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
Mark P MolloyAustralian Proteome Analysis Facility (APAF), Department of Chemistry & Biomolecular Sciences, Macquarie University, Sydney, NSW, Australia. m.molloy@sydney.edu.au.ORCID http://orcid.org/0000-0003-4679-5868
The University of Sydney · AUAGRF Ltd · AUQIMR Berghofer Medical Research Institute · AUUniversität Hamburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGenotyping of melanomas is used to identify patients for treatment with BRAF and MEK inhibitors, but clinical responses are highly variable. This study investigated the utility of protein expression phenotyping to provide an integrated assessment of gene expression programs in BRAF/NRAS melanoma which would be useful for prognosis and may predict response to MEK inhibition.

methodsMass spectrometry profiling of early passage cell lines established from Stage III cutaneous melanomas was conducted. Basal protein expression was correlated with in vitro response to the MEK inhibitor, selumetinib. Protein expression in a cohort of 32 drug naïve BRAF/NRAS metastatic melanoma specimens was examined. The prognostic utility of a subset of these proteins and mRNA transcripts from a separate cohort was determined.

resultsUnsupervised analysis of basal cell line protein abundances delineated response to selumetinib, but BRAF/NRAS genotype did not. Resistance was associated with functions including cell motility, cell adhesion and cytoskeletal organization. Several of these response biomarkers were observed in lymph node biospecimens and correlated with melanoma-specific survival. Loss of ICAM-1 protein and mRNA expression was a strong prognosticator of diminished survival in BRAF/NRAS mutant melanoma.

conclusionsThese results demonstrate the utility of proteomic phenotyping to identify both putative biomarkers of response to MEK inhibition and prognostication associated with metastatic melanoma.

Indexed as

MutationBenzimidazolesCell Line, TumorChromatography, LiquidCohort StudiesCutaneous Malignant MelanomaFemaleGTP PhosphohydrolasesHumansIntercellular Adhesion Molecule-1MaleMelanomaMembrane ProteinsNeoplasm StagingPrognosisProtein Kinase InhibitorsAZD 6244BenzimidazolesBRAF protein, humanGTP PhosphohydrolasesICAM1 protein, humanIntercellular Adhesion Molecule-1Membrane ProteinsNRAS protein, humanProtein Kinase InhibitorsProto-Oncogene Proteins B-raf

Identifiers

PMID30116025
PMCPMC6173697
OpenAlexW2885690582

What OpenQuestion holds

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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.