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

BMC Cancer

Jean-Pierre Roperch⁵  Roberto Incitti⁶  Solène Forbin⁴  Floriane Bard⁴  Hicham Mansour⁴  Farida Mesli¹  Isabelle Baumgaertner²  Francesco Brunetti³  Iradj Sobhani¹ 

[1] Department of Gastroenterology and Medical Oncology, Henri Mondor Hospital, Créteil, France

[2] Department of Clinical Oncology, Henri Mondor Hospital, Créteil, France

[3] Department of Surgery, Henri Mondor Hospital, Créteil, France

[4] Laboratoire d’Investigation Clinique (LIC), Henri Mondor Hospital & University Paris-Est, Créteil, France

[5] Profilome SAS, Paris Biotech 24 rue du Faubourg St Jacques, Paris 75014, France

[6] King Abdullah University of Science and Technology (KAUST), Biosciences Core Laboratory, Thuwal 23955-6900, Saudi Arabia

关键词: Epigenetic markers;    QM-MSP;    Circulating DNA methylation;    Colorectal cancer;   

Others  :  859232
DOI  :  10.1186/1471-2407-13-566

 received in 2013-08-05, accepted in 2013-11-25,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Roperch et al.; licensee BioMed Central Ltd.

【 图 表 】

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