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dc.contributor.authorAlderdice, M
dc.contributor.authorCraig, SG
dc.contributor.authorHumphries, MP
dc.contributor.authorGilmore, A
dc.contributor.authorJohnston, N
dc.contributor.authorBingham, V
dc.contributor.authorCoyle, V
dc.contributor.authorSenevirathne, S
dc.contributor.authorLongley, DB
dc.contributor.authorLoughrey, MB
dc.contributor.authorMcQuaid, S
dc.contributor.authorJames, JA
dc.contributor.authorSalto-Tellez, M
dc.contributor.authorLawler, M
dc.contributor.authorMcArt, DG
dc.date.accessioned2021-05-24T08:21:09Z
dc.date.available2021-05-24T08:21:09Z
dc.identifier.citationNAR genomics and bioinformatics, 2021, 3 (2), pp. lqab016 - ?
dc.identifier.issn2631-9268
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4573
dc.identifier.eissn2631-9268
dc.identifier.eissn2631-9268en_US
dc.identifier.doi10.1093/nargab/lqab016
dc.identifier.doi10.1093/nargab/lqab016en_US
dc.description.abstractIdentifying robust predictive biomarkers to stratify colorectal cancer (CRC) patients based on their response to immune-checkpoint therapy is an area of unmet clinical need. Our evolutionary algorithm Atlas Correlation Explorer (ACE) represents a novel approach for mining The Cancer Genome Atlas (TCGA) data for clinically relevant associations. We deployed ACE to identify candidate predictive biomarkers of response to immune-checkpoint therapy in CRC. We interrogated the colon adenocarcinoma (COAD) gene expression data across nine immune-checkpoints (<i>PDL1, PDCD1, CTLA4, LAG3, TIM3, TIGIT, ICOS, IDO1</i> and <i>BTLA</i>). <i>IL2RB</i> was identified as the most common gene associated with immune-checkpoint genes in CRC. Using human/murine single-cell RNA-seq data, we demonstrated that <i>IL2RB</i> was expressed predominantly in a subset of T-cells associated with increased immune-checkpoint expression (<i>P</i> < 0.0001). Confirmatory IL2RB immunohistochemistry (IHC) analysis in a large MSI-H colon cancer tissue microarray (TMA; <i>n</i> = 115) revealed sensitive, specific staining of a subset of lymphocytes and a strong association with FOXP3+ lymphocytes (<i>P</i> < 0.0001). <i>IL2RB</i> mRNA positively correlated with three previously-published gene signatures of response to immune-checkpoint therapy (<i>P</i> < 0.0001). Our evolutionary algorithm has identified <i>IL2RB</i> to be extensively linked to immune-checkpoints in CRC; its expression should be investigated for clinical utility as a potential predictive biomarker for CRC patients receiving immune-checkpoint blockade.
dc.formatElectronic-eCollection
dc.format.extentlqab016 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleEvolutionary genetic algorithm identifies <i>IL2RB</i> as a potential predictive biomarker for immune-checkpoint therapy in colorectal cancer.
dc.typeJournal Article
dcterms.dateAccepted2021-03-26
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1093/nargab/lqab016
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNAR genomics and bioinformatics
pubs.issue2
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Integrated Pathology
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Integrated Pathology
pubs.publication-statusAccepted
pubs.volume3en_US
pubs.embargo.termsNot known
icr.researchteamIntegrated Pathology
icr.researchteamIntegrated Pathologyen_US
dc.contributor.icrauthorSalto-Tellez, Manuelen


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