Abstract
BackgroundIn 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™ for the detection of ctDNA in CRCs.MethodsDetection of hypermethylated NPY and WIF1 was developed on Cristal digital PCR™. 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).ResultsThe 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.ConclusionUsing Crystal digital PCR™, this study shows that hypermethylation of NPY and WIF1 are constant specific biomarkers of CRCs regardless of a potential role in carcinogenesis.
Highlights
Colorectal cancer (CRC) is the third most common cancer worldwide with more than one million new cases diagnosed every year
Patients Digital PCR analyses were conducted on blood and tissue samples from patients with CRC treated at the University Hospital of Besancon (France) (Table 1)
We developed a 2-panel assay targeting these biomarkers previously described on a Naica Crystal Digital PCR systemTM (Stilla Technonologies, Villejuif, France)
Summary
Colorectal cancer (CRC) is the third most common cancer worldwide with more than one million new cases diagnosed every year. The effectiveness of targeted therapies is based on mutational profiles of RAS/MAPK pathway genes [1] These mutations are typically sought at the time of diagnosis from a cancer tissue biopsy. In cases of a non-feasible biopsy, this search can be performed on circulating tumor DNA (ctDNA). The liquid biopsy is a non-invasive approach and can be repeated over time to perform dynamic monitoring of tumors. 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. The objective of this work is to develop the research of hypermethylation of NPY and WIF1 by Crystal Digital PCRTM for the detection of ctDNA in CRCs
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