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dc.contributor.authorRagulan, C
dc.contributor.authorEason, K
dc.contributor.authorFontana, E
dc.contributor.authorNyamundanda, G
dc.contributor.authorTarazona, N
dc.contributor.authorPatil, Y
dc.contributor.authorPoudel, P
dc.contributor.authorLawlor, RT
dc.contributor.authorDel Rio, M
dc.contributor.authorKoo, S-L
dc.contributor.authorTan, W-S
dc.contributor.authorSclafani, F
dc.contributor.authorBegum, R
dc.contributor.authorTeixeira Mendes, LS
dc.contributor.authorMartineau, P
dc.contributor.authorScarpa, A
dc.contributor.authorCervantes, A
dc.contributor.authorTan, IB
dc.contributor.authorCunningham, D
dc.contributor.authorSadanandam, A
dc.date.accessioned2020-06-03T14:22:32Z
dc.date.issued2019-05-21
dc.identifier.citationScientific reports, 2019, 9 (1), pp. 7665 - ?
dc.identifier.issn2045-2322
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3695
dc.identifier.eissn2045-2322
dc.identifier.doi10.1038/s41598-019-43492-0
dc.description.abstractPreviously, we classified colorectal cancers (CRCs) into five CRCAssigner (CRCA) subtypes with different prognoses and potential treatment responses, later consolidated into four consensus molecular subtypes (CMS). Here we demonstrate the analytical development and validation of a custom NanoString nCounter platform-based biomarker assay (NanoCRCA) to stratify CRCs into subtypes. To reduce costs, we switched from the standard nCounter protocol to a custom modified protocol. The assay included a reduced 38-gene panel that was selected using an in-house machine-learning pipeline. We applied NanoCRCA to 413 samples from 355 CRC patients. From the fresh frozen samples (n = 237), a subset had matched microarray/RNAseq profiles (n = 47) or formalin-fixed paraffin-embedded (FFPE) samples (n = 58). We also analyzed a further 118 FFPE samples. We compared the assay results with the CMS classifier, different platforms (microarrays/RNAseq) and gene-set classifiers (38 and the original 786 genes). The standard and modified protocols showed high correlation (> 0.88) for gene expression. Technical replicates were highly correlated (> 0.96). NanoCRCA classified fresh frozen and FFPE samples into all five CRCA subtypes with consistent classification of selected matched fresh frozen/FFPE samples. We demonstrate high and significant subtype concordance across protocols (100%), gene sets (95%), platforms (87%) and with CMS subtypes (75%) when evaluated across multiple datasets. Overall, our NanoCRCA assay with further validation may facilitate prospective validation of CRC subtypes in clinical trials and beyond.
dc.formatElectronic
dc.format.extent7665 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectColorectal Neoplasms
dc.subjectOligonucleotide Array Sequence Analysis
dc.subjectTissue Array Analysis
dc.subjectGene Expression Profiling
dc.subjectBiomarkers, Tumor
dc.titleAnalytical Validation of Multiplex Biomarker Assay to Stratify Colorectal Cancer into Molecular Subtypes.
dc.typeJournal Article
dcterms.dateAccepted2019-04-23
rioxxterms.versionofrecord10.1038/s41598-019-43492-0
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2019-05-21
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfScientific reports
pubs.issue1
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/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Systems and Precision Cancer Medicine
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
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/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Systems and Precision Cancer Medicine
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume9
pubs.embargo.termsNot known
icr.researchteamMedicine (RMH Smith Cunningham)en_US
icr.researchteamSystems and Precision Cancer Medicineen_US
dc.contributor.icrauthorFontana, Elisaen
dc.contributor.icrauthorCunningham, Daviden
dc.contributor.icrauthorSadanandam, Angurajen
dc.contributor.icrauthorEason, Katherineen


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