Evidence map›Paper›PMID 32300895›Full record

ArticleMetabolomics : Official journal of the Metabolomic Society2020

Metabolic characterization of colorectal cancer cells harbouring different KRAS mutations in codon 12, 13, 61 and 146 using human SW48 isogenic cell lines.

Dorna Varshavi, Dorsa Varshavi, Nicola McCarthy, Kirill Veselkov, Hector C Keun, Jeremy R Everett

Open access · hybridAbstract read
In one paragraph

Article in Metabolomics : Official journal of the Metabolomic Society, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing 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

26 citing papers in PubMed, 41 citations in OpenAlex.

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  13. KRAS Mutation Detection with (2Molecular pharmaceutics · 2024
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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

6 authors at 4 institutions in 1 country.

Dorna VarshaviMedway Metabonomics Research Group, University of Greenwich, Chatham Maritime, Kent, ME4 4TB, UK.
Dorsa VarshaviMedway Metabonomics Research Group, University of Greenwich, Chatham Maritime, Kent, ME4 4TB, UK.
Nicola McCarthyHorizon Discovery Ltd., Cambridge Research Park, 8100 Beach Dr, Waterbeach, Cambridge, CB25 9TL, UK.ORCID 0000-0001-6990-3943
Kirill VeselkovDepartment of Surgery and Cancer, Faculty of Medicine, Imperial College, London, SW7 2AZ, UK.
Hector C KeunDepartment of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London, W12 ONN, UK.
Jeremy R EverettMedway Metabonomics Research Group, University of Greenwich, Chatham Maritime, Kent, ME4 4TB, UK. j.r.everett@greenwich.ac.uk.ORCID 0000-0003-1550-4482
University of Greenwich · GBHammersmith Hospital · GBHorizon Discovery (United Kingdom) · GBImperial College London · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionKirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) mutations occur in approximately one-third of colorectal (CRC) tumours and have been associated with poor prognosis and resistance to some therapeutics. In addition to the well-documented pro-tumorigenic role of mutant Ras alleles, there is some evidence suggesting that not all KRAS mutations are equal and the position and type of amino acid substitutions regulate biochemical activity and transforming capacity of KRAS mutations.

objectivesTo investigate the metabolic signatures associated with different KRAS mutations in codons 12, 13, 61 and 146 and to determine what metabolic pathways are affected by different KRAS mutations.

methodsWe applied an NMR-based metabonomics approach to compare the metabolic profiles of the intracellular extracts and the extracellular media from isogenic human SW48 CRC cell lines with different KRAS mutations in codons 12 (G12D, G12A, G12C, G12S, G12R, G12V), 13 (G13D), 61 (Q61H) and 146 (A146T) with their wild-type counterpart. We used false discovery rate (FDR)-corrected analysis of variance (ANOVA) to determine metabolites that were statistically significantly different in concentration between the different mutants.

resultsCRC cells carrying distinct KRAS mutations exhibited differential metabolic remodelling, including differences in glycolysis, glutamine utilization and in amino acid, nucleotide and hexosamine metabolism.

conclusionsMetabolic differences among different KRAS mutations might play a role in their different responses to anticancer treatments and hence could be exploited as novel metabolic vulnerabilities to develop more effective therapies against oncogenic KRAS.

Indexed as

MutationColorectal NeoplasmsHumansMetabolomicsProto-Oncogene Proteins p21(ras)Tumor Cells, CulturedKRAS protein, humanProto-Oncogene Proteins p21(ras)Colorectal cancerKRASMetabolic profilingMetabolomicsMetabonomicsMutationsNMR

Identifiers

PMID32300895
PMCPMC7162829
OpenAlexW3016882581

What OpenQuestion holds

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LicenceCC BY
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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.