The detection of the methylated Wif-1 gene is more accurate than a fecal occult blood test for colorectal cancer screening

Handle URI:
http://hdl.handle.net/10754/334640
Title:
The detection of the methylated Wif-1 gene is more accurate than a fecal occult blood test for colorectal cancer screening
Authors:
Amiot, Aurelien; Mansour, Hicham; Baumgaertner, Isabelle; Delchier, Jean-Charles; Tournigand, Christophe; Furet, Jean-Pierre; Carrau, Jean-Pierre; Canoui-Poitrine, Florence; Sobhani, Iradj
Abstract:
Background: The clinical benefit of guaiac fecal occult blood tests (FOBT) is now well established for colorectal cancer screening. Growing evidence has demonstrated that epigenetic modifications and fecal microbiota changes, also known as dysbiosis, are associated with CRC pathogenesis and might be used as surrogate markers of CRC. Patients and Methods: We performed a cross-sectional study that included all consecutive subjects that were referred (from 2003 to 2007) for screening colonoscopies. Prior to colonoscopy, effluents (fresh stools, sera-S and urine-U) were harvested and FOBTs performed. Methylation levels were measured in stools, S and U for 3 genes (Wif1, ALX-4, and Vimentin) selected from a panel of 63 genes; Kras mutations and seven dominant and subdominant bacterial populations in stools were quantified. Calibration was assessed with the Hosmer-Lemeshow chi-square, and discrimination was determined by calculating the C-statistic (Area Under Curve) and Net Reclassification Improvement index. Results: There were 247 individuals (mean age 60.8±12.4 years, 52% of males) in the study group, and 90 (36%) of these individuals were patients with advanced polyps or invasive adenocarcinomas. A multivariate model adjusted for age and FOBT led to a C-statistic of 0.83 [0.77-0.88]. After supplementary sequential (one-by-one) adjustment, Wif-1 methylation (S or U) and fecal microbiota dysbiosis led to increases of the C-statistic to 0.90 [0.84-0.94] (p = 0.02) and 0.81 [0.74-0.86] (p = 0.49), respectively. When adjusted jointly for FOBT and Wif-1 methylation or fecal microbiota dysbiosis, the increase of the C-statistic was even more significant (0.91 and 0.85, p<0.001 and p = 0.10, respectively). Conclusion: The detection of methylated Wif-1 in either S or U has a higher performance accuracy compared to guaiac FOBT for advanced colorectal neoplasia screening. Conversely, fecal microbiota dysbiosis detection was not more accurate. Blood and urine testing could be used in those individuals reluctant to undergo stool testing. © 2014 Amiot et al.
Citation:
Amiot A, Mansour H, Baumgaertner I, Delchier J-C, Tournigand C, et al. (2014) The Detection of the Methylated Wif-1 Gene Is More Accurate than a Fecal Occult Blood Test for Colorectal Cancer Screening. PLoS ONE 9: e99233. doi:10.1371/journal.pone.0099233.
Publisher:
Public Library of Science (PLoS)
Journal:
PLoS ONE
Issue Date:
15-Jul-2014
DOI:
10.1371/journal.pone.0099233
PubMed ID:
25025467
PubMed Central ID:
PMC4099003
Type:
Article
ISSN:
19326203
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorAmiot, Aurelienen
dc.contributor.authorMansour, Hichamen
dc.contributor.authorBaumgaertner, Isabelleen
dc.contributor.authorDelchier, Jean-Charlesen
dc.contributor.authorTournigand, Christopheen
dc.contributor.authorFuret, Jean-Pierreen
dc.contributor.authorCarrau, Jean-Pierreen
dc.contributor.authorCanoui-Poitrine, Florenceen
dc.contributor.authorSobhani, Iradjen
dc.date.accessioned2014-11-11T14:33:16Z-
dc.date.available2014-11-11T14:33:16Z-
dc.date.issued2014-07-15en
dc.identifier.citationAmiot A, Mansour H, Baumgaertner I, Delchier J-C, Tournigand C, et al. (2014) The Detection of the Methylated Wif-1 Gene Is More Accurate than a Fecal Occult Blood Test for Colorectal Cancer Screening. PLoS ONE 9: e99233. doi:10.1371/journal.pone.0099233.en
dc.identifier.issn19326203en
dc.identifier.pmid25025467en
dc.identifier.doi10.1371/journal.pone.0099233en
dc.identifier.urihttp://hdl.handle.net/10754/334640en
dc.description.abstractBackground: The clinical benefit of guaiac fecal occult blood tests (FOBT) is now well established for colorectal cancer screening. Growing evidence has demonstrated that epigenetic modifications and fecal microbiota changes, also known as dysbiosis, are associated with CRC pathogenesis and might be used as surrogate markers of CRC. Patients and Methods: We performed a cross-sectional study that included all consecutive subjects that were referred (from 2003 to 2007) for screening colonoscopies. Prior to colonoscopy, effluents (fresh stools, sera-S and urine-U) were harvested and FOBTs performed. Methylation levels were measured in stools, S and U for 3 genes (Wif1, ALX-4, and Vimentin) selected from a panel of 63 genes; Kras mutations and seven dominant and subdominant bacterial populations in stools were quantified. Calibration was assessed with the Hosmer-Lemeshow chi-square, and discrimination was determined by calculating the C-statistic (Area Under Curve) and Net Reclassification Improvement index. Results: There were 247 individuals (mean age 60.8±12.4 years, 52% of males) in the study group, and 90 (36%) of these individuals were patients with advanced polyps or invasive adenocarcinomas. A multivariate model adjusted for age and FOBT led to a C-statistic of 0.83 [0.77-0.88]. After supplementary sequential (one-by-one) adjustment, Wif-1 methylation (S or U) and fecal microbiota dysbiosis led to increases of the C-statistic to 0.90 [0.84-0.94] (p = 0.02) and 0.81 [0.74-0.86] (p = 0.49), respectively. When adjusted jointly for FOBT and Wif-1 methylation or fecal microbiota dysbiosis, the increase of the C-statistic was even more significant (0.91 and 0.85, p<0.001 and p = 0.10, respectively). Conclusion: The detection of methylated Wif-1 in either S or U has a higher performance accuracy compared to guaiac FOBT for advanced colorectal neoplasia screening. Conversely, fecal microbiota dysbiosis detection was not more accurate. Blood and urine testing could be used in those individuals reluctant to undergo stool testing. © 2014 Amiot et al.en
dc.language.isoenen
dc.publisherPublic Library of Science (PLoS)en
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.rightsArchived with thanks to PLoS ONEen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleThe detection of the methylated Wif-1 gene is more accurate than a fecal occult blood test for colorectal cancer screeningen
dc.typeArticleen
dc.identifier.journalPLoS ONEen
dc.identifier.pmcidPMC4099003en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorMansour, Hichamen

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