Aberrant methylation of NPY, PENK, and WIF1 as a promising marker for blood-based diagnosis of colorectal cancer
KAUST DepartmentComputational Bioscience Research Center (CBRC)
Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Bioscience Core Lab
MetadataShow full item record
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.
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.
PubMed Central IDPMC4219483
The following license files are associated with this item:
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.
- Detection of promoter hypermethylation of Wnt antagonist genes in fecal samples for diagnosis of early colorectal cancer.
- Authors: Zhang H, Zhu YQ, Wu YQ, Zhang P, Qi J
- Issue date: 2014 May 28
- Comparative analysis of PCR-based biomarker assay methods for colorectal polyp detection from fecal DNA.
- Authors: Ausch C, Kim YH, Tsuchiya KD, Dzieciatkowski S, Washington MK, Paraskeva C, Radich J, Grady WM
- Issue date: 2009 Aug
- DNA methylation of phosphatase and actin regulator 3 detects colorectal cancer in stool and complements FIT.
- Authors: Bosch LJ, Oort FA, Neerincx M, Khalid-de Bakker CA, Terhaar sive Droste JS, Melotte V, Jonkers DM, Masclee AA, Mongera S, Grooteclaes M, Louwagie J, van Criekinge W, Coupé VM, Mulder CJ, van Engeland M, Carvalho B, Meijer GA
- Issue date: 2012 Mar
- Detection of aberrant promoter methylation of GSTP1, RASSF1A, and RARβ2 in serum DNA of patients with breast cancer by a newly established one-step methylation-specific PCR assay.
- Authors: Yamamoto N, Nakayama T, Kajita M, Miyake T, Iwamoto T, Kim SJ, Sakai A, Ishihara H, Tamaki Y, Noguchi S
- Issue date: 2012 Feb
- Aberrant methylation of APC, MGMT, RASSF2A, and Wif-1 genes in plasma as a biomarker for early detection of colorectal cancer.
- Authors: Lee BB, Lee EJ, Jung EH, Chun HK, Chang DK, Song SY, Park J, Kim DH
- Issue date: 2009 Oct 1