Aberrant methylation of NPY, PENK, and WIF1 as a promising marker for blood-based diagnosis of colorectal cancer

Handle URI:
http://hdl.handle.net/10754/334522
Title:
Aberrant methylation of NPY, PENK, and WIF1 as a promising marker for blood-based diagnosis of colorectal cancer
Authors:
Roperch, J.-P.; Incitti, R.; Forbin, S.; Bard, F.; Mansour, H.; Mesli, F.; Baumgaertner, I.; Brunetti, F.; Sobhani, I.
Abstract:
Background: 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.
KAUST Department:
Biosciences Core Lab
Citation:
Roperch 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.
Publisher:
BioMed Central
Journal:
BMC Cancer
Issue Date:
1-Dec-2013
DOI:
10.1186/1471-2407-13-566
PubMed ID:
24289328
PubMed Central ID:
PMC4219483
Type:
Article
ISSN:
14712407
Appears in Collections:
Articles; Biosciences Core Lab

Full metadata record

DC FieldValue Language
dc.contributor.authorRoperch, J.-P.en
dc.contributor.authorIncitti, R.en
dc.contributor.authorForbin, S.en
dc.contributor.authorBard, F.en
dc.contributor.authorMansour, H.en
dc.contributor.authorMesli, F.en
dc.contributor.authorBaumgaertner, I.en
dc.contributor.authorBrunetti, F.en
dc.contributor.authorSobhani, I.en
dc.date.accessioned2014-11-11T14:28:16Z-
dc.date.available2014-11-11T14:28:16Z-
dc.date.issued2013-12-01en
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.en
dc.identifier.issn14712407en
dc.identifier.pmid24289328en
dc.identifier.doi10.1186/1471-2407-13-566en
dc.identifier.urihttp://hdl.handle.net/10754/334522en
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.en
dc.language.isoenen
dc.publisherBioMed Centralen
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.en
dc.rightsArchived with thanks to BMC Canceren
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/en
dc.subjectCirculating DNA methylationen
dc.subjectColorectal canceren
dc.subjectEpigenetic markersen
dc.subjectQM-MSPen
dc.subjectadulten
dc.subjectageden
dc.subjectblood samplingen
dc.subjectclinical articleen
dc.subjectcolonoscopyen
dc.subjectcolorectal canceren
dc.subjectcontrolled studyen
dc.subjectdiagnostic test accuracy studyen
dc.subjectDNA methylationen
dc.subjectepigeneticsen
dc.subjectgeneen
dc.subjecthuman cellen
dc.subjecthuman tissueen
dc.subjectmiddle ageden
dc.subjectNPY geneen
dc.subjectpathologyen
dc.subjectPENK geneen
dc.subjectreceiver operating characteristicen
dc.subjectsensitivity and specificityen
dc.subjectvery elderlyen
dc.subjectWIF1 geneen
dc.subjectAdaptor Proteins, Signal Transducingen
dc.subjectAdenocarcinomaen
dc.subjectAgeden
dc.subjectAged, 80 and overen
dc.subjectCase-Control Studiesen
dc.subjectColorectal Neoplasmsen
dc.subjectDNAen
dc.subjectDNA Methylationen
dc.subjectEnkephalinsen
dc.subjectMiddle Ageden
dc.subjectMolecular Diagnostic Techniquesen
dc.subjectMultiplex Polymerase Chain Reactionen
dc.subjectNeoplasm Stagingen
dc.subjectNeuropeptide Yen
dc.subjectPromoter Regions, Geneticen
dc.subjectProtein Precursorsen
dc.subjectRepressor Proteinsen
dc.subjectROC Curveen
dc.subjectSequence Analysis, DNAen
dc.subjectTumor Markers, Biologicalen
dc.titleAberrant methylation of NPY, PENK, and WIF1 as a promising marker for blood-based diagnosis of colorectal canceren
dc.typeArticleen
dc.contributor.departmentBiosciences Core Laben
dc.identifier.journalBMC Canceren
dc.identifier.pmcidPMC4219483en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionProfilome SAS, Paris Biotech, 24 rue du Faubourg St Jacques, Paris 75014, Franceen
dc.contributor.institutionLaboratoire d'Investigation Clinique (LIC), Henri Mondor Hospital and University Paris-Est, Crteil, Franceen
dc.contributor.institutionDepartment of Gastroenterology and Medical Oncology, Henri Mondor Hospital, Crteil, Franceen
dc.contributor.institutionDepartment of Clinical Oncology, Henri Mondor Hospital, Crteil, Franceen
dc.contributor.institutionDepartment of Surgery, Henri Mondor Hospital, Crteil, Franceen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorIncitti, Robertoen
kaust.authorMansour, Hichamen

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