The detection of specific hypermethylated WIF1 and NPY genes in circulating DNA by crystal digital PCR™ is a powerful new tool for colorectal cancer diagnosis and screening

Background In oncology, liquid biopsy is of major relevance from theranostic point of view. The searching for mutations in circulating tumor DNA (ctDNA) in case of colorectal cancers (CRCs) allows the optimization of patient care. In this context, independent of mutation status biomarkers are requir...

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Bibliographic Details
Published in:BMC cancer 2021-10, Vol.21 (1), p.1-1092, Article 1092
Main Authors: Overs, Alexis, Flammang, Mylène, Hervouet, Eric, Bermont, Laurent, Pretet, Jean-Luc, Christophe, Borg, Selmani, Zohair
Format: Article
Language:English
Subjects:
Biomarkers
Biopsy
Blood & organ donations
Carcinogenesis
Colorectal cancer
Colorectal carcinoma
Deoxyribonucleic acid
Development and progression
DNA
DNA methylation
Epigenetic inheritance
Epigenetics
Gene expression
Genetic aspects
Health aspects
Identification and classification
Life Sciences
Liquid biopsy
Methylation
Mutation
Neuropeptide Y
NPY
Patients
Polymerase chain reaction
Software
Tumors
WIF1
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Summary:Background In oncology, liquid biopsy is of major relevance from theranostic point of view. The searching for mutations in circulating tumor DNA (ctDNA) in case of colorectal cancers (CRCs) allows the optimization of patient care. In this context, independent of mutation status biomarkers are required for its detection to confirm the presence of ctDNA in liquid biopsies. Indeed, the hypermethylation of NPY and WIF1 genes appear to be an ideal biomarker for the specific detection of ctDNA in CRCs. The objective of this work is to develop the research of hypermethylation of NPY and WIF1 by Crystal Digital PCR[TM] for the detection of ctDNA in CRCs. Methods Detection of hypermethylated NPY and WIF1 was developed on Cristal digital PCR[TM]. Biological validation was performed from a local cohort of 22 liquid biopsies and 23 tissue samples from patients with CRC. These patients were treated at the University Hospital of Besancon (France). Results The local cohort study confirmed that NPY and WIF1 were significantly hypermethylated in tumor tissues compared to adjacent non-tumor tissues (WIF1 p < 0.001; NPY p < 0.001; non-parametric Wilcoxon paired-series test). Histological characteristics, tumor stages or mutation status were not correlated to the methylation profiles. On the other hand, hypermethylation of NPY or WIF1 in liquid biopsy had a 95.5% [95%CI 77-100%] sensitivity and 100% [95%CI 69-100%] specificity. Conclusion Using Crystal digital PCR[TM], this study shows that hypermethylation of NPY and WIF1 are constant specific biomarkers of CRCs regardless of a potential role in carcinogenesis. Keywords: Colorectal cancer, Liquid biopsy, Epigenetics, DNA methylation, NPY, WIF1, Digital PCR
ISSN:1471-2407
1471-2407
DOI:10.1186/s12885-021-08816-2