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dc.contributor.authorRoperch, J.-P.
dc.contributor.authorIncitti, Roberto
dc.contributor.authorForbin, S.
dc.contributor.authorBard, F.
dc.contributor.authorMansour, Hicham
dc.contributor.authorMesli, F.
dc.contributor.authorBaumgaertner, I.
dc.contributor.authorBrunetti, F.
dc.contributor.authorSobhani, I.
dc.date.accessioned2014-11-11T14:28:16Z
dc.date.available2014-11-11T14:28:16Z
dc.date.issued2013-12-01
dc.identifier.citationRoperch J-P, Incitti R, Forbin S, Bard F, Mansour H, et al. (2013) Aberrant methylation of NPY, PENK, and WIF1 as a promising marker for blood-based diagnosis of colorectal cancer. BMC Cancer 13: 566. doi:10.1186/1471-2407-13-566.
dc.identifier.issn14712407
dc.identifier.pmid24289328
dc.identifier.doi10.1186/1471-2407-13-566
dc.identifier.urihttp://hdl.handle.net/10754/334522
dc.description.abstractBackground: DNA methylation is a well-known epigenetic mechanism involved in epigenetic gene regulation. Several genes were reported hypermethylated in CRC, althought no gene marker was proven to be individually of sufficient sensitivity or specificity in routine clinical practice. Here, we identified novel epigenetic markers and assessed their combined use for diagnostic accuracy.Methods: We used methylation arrays on samples from several effluents to characterize methylation profiles in CRC samples and controls, as established by colonoscopy and pathology findings, and selected two differentially methylated candidate epigenetic genes (NPY, PENK). To this gene panel we added WIF, on the basis of being reported in literature as silenced by promoter hypermethylation in several cancers, including CRC. We measured their methylation degrees by quantitative multiplex-methylation specific PCR (QM-MSP) on 15 paired carcinomas and adjacent non-cancerous colorectal tissues and we subsequently performed a clinical validation on two different series of 266 serums, subdivided in 32 CRC, 26 polyps, 47 other cancers and 161 with normal colonoscopy. We assessed the results by receiver operating characteristic curve (ROC), using cumulative methylation index (CMI) as variable threshold.Results: We obtained CRC detection on tissues with both sensitivity and specificity of 100%. On serum CRC samples, we obtained sensitivity/specificity values of, e.g., 87%/80%, 78%/90% and 59%/95%, and negative predictive value/positive predictive value figures of 97%/47%, 95%/61% and 92%/70%. On serum samples from other cancers we obtained sensitivity/specificity of, e.g, 89%/25%, 43%/80% and 28%/91%.Conclusions: We showed the potential of NPY, PENK, and WIF1 as combined epigenetic markers for CRC diagnosis, both in tissue and serum and tested their use as serum biomarkers in other cancers. We optimized a QM-MSP for simultaneously quantifying their methylation levels. Our assay can be an effective blood test for patients where CRC risk is present but difficult to assess (e.g. mild symptoms with no CRC family history) and who would therefore not necessarily choose to go for further examination. This panel of markers, if validated, can also be a cost effective screening tool for the detection of asymptomatic cancer patients for colonoscopy.
dc.language.isoen
dc.publisherSpringer Nature
dc.rightsThis is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.rightsArchived with thanks to BMC Cancer
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/
dc.subjectCirculating DNA methylation
dc.subjectColorectal cancer
dc.subjectEpigenetic markers
dc.subjectQM-MSP
dc.subjectadult
dc.subjectaged
dc.subjectblood sampling
dc.subjectclinical article
dc.subjectcolonoscopy
dc.subjectcolorectal cancer
dc.subjectcontrolled study
dc.subjectdiagnostic test accuracy study
dc.subjectDNA methylation
dc.subjectepigenetics
dc.subjectgene
dc.subjecthuman cell
dc.subjecthuman tissue
dc.subjectmiddle aged
dc.subjectNPY gene
dc.subjectpathology
dc.subjectPENK gene
dc.subjectreceiver operating characteristic
dc.subjectsensitivity and specificity
dc.subjectvery elderly
dc.subjectWIF1 gene
dc.subjectAdaptor Proteins, Signal Transducing
dc.subjectAdenocarcinoma
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectCase-Control Studies
dc.subjectColorectal Neoplasms
dc.subjectDNA
dc.subjectDNA Methylation
dc.subjectEnkephalins
dc.subjectMiddle Aged
dc.subjectMolecular Diagnostic Techniques
dc.subjectMultiplex Polymerase Chain Reaction
dc.subjectNeoplasm Staging
dc.subjectNeuropeptide Y
dc.subjectPromoter Regions, Genetic
dc.subjectProtein Precursors
dc.subjectRepressor Proteins
dc.subjectROC Curve
dc.subjectSequence Analysis, DNA
dc.subjectTumor Markers, Biological
dc.titleAberrant methylation of NPY, PENK, and WIF1 as a promising marker for blood-based diagnosis of colorectal cancer
dc.typeArticle
dc.contributor.departmentBioscience Core Lab
dc.contributor.departmentComputational Bioscience Research Center (CBRC)
dc.contributor.departmentComputer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
dc.identifier.journalBMC Cancer
dc.identifier.pmcidPMC4219483
dc.eprint.versionPublisher's Version/PDF
dc.contributor.institutionProfilome SAS, Paris Biotech, 24 rue du Faubourg St Jacques, Paris 75014, France
dc.contributor.institutionLaboratoire d'Investigation Clinique (LIC), Henri Mondor Hospital and University Paris-Est, Crteil, France
dc.contributor.institutionDepartment of Gastroenterology and Medical Oncology, Henri Mondor Hospital, Crteil, France
dc.contributor.institutionDepartment of Clinical Oncology, Henri Mondor Hospital, Crteil, France
dc.contributor.institutionDepartment of Surgery, Henri Mondor Hospital, Crteil, France
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)
kaust.personIncitti, Roberto
kaust.personMansour, Hicham
refterms.dateFOA2018-06-13T15:44:59Z
dc.date.published-online2013-12-01
dc.date.published-print2013-12


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This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Except where otherwise noted, this item's license is described as This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.