Publications
2025
- Impact Factor < 5Dynamic DNA methylation changes during colorectal oncogenesis with insights from adenoma stagesScientific Report, Nov 2025
The dynamics of colorectal epigenetics within the adenoma stages of oncogenesis remain undocumented. In this study, we investigated DNA methylation dynamics in colorectal cancer oncogenesis from non-tumor colon tissue to low-grade, high-grade adenoma and adenocarcinoma. The methylome of 12 low-grade and 19 high-grade colorectal adenomas was determined via the EPIC v1 Human Methylation BeadChip. These methylation profiles were complemented with the methylomes of 206 non-tumor colon and 22 colon adenocarcinoma samples from the GEO and TCGA databases. Differentially methylated CpGs were identified via Student’s t test and used to monitor the evolution of the colon methylome during oncogenesis. The differentially methylated promoters were used to infer the associated biological process via gene ontology and the evolution of the methylation of 34 described colorectal cancer DNA methylation biomarkers was explored. A total of 11.9% of the colon methylome was significantly altered (q < 10(- 4)) during oncogenesis, with half corresponding to DNA demethylation. Of which, 67.4% occurred during the transition from non-tumor colon tissue to low-grade adenoma. A total of 9% of the DNA methylation changes were specific to low-grade and/or high-grade adenomas. The biological pathways related to the sensory perception of odor and stimulus were hypomethylated early, nucleic acid metabolic process were methylated early, post-transcriptional regulation were transiently hypomethylated and mitotic cell cycle were transiently methylated. Twenty-one out of 34 the biomarkers were methylated in low-grade adenomas and 11 out of 34 in high-grade adenomas. This suggests that they could be used to distinguish stages of oncogenesis. This study provides insight into the dynamics of colonic epigenetics during oncogenesis, with early DNA methylation changes in low-grade adenomas associated with transient DNA methylation changes. However, the causality of these changes remains to be elucidated. This study also explores the evolution of known biomarkers and their clinical applications for indirectly asserting the tumor’s stage.
2024
- Impact Factor < 5COL25A1 and METAP1D DNA methylation are promising liquid biopsy epigenetic biomarkers of colorectal cancer using digital PCR.Clinical Epigenetics, Oct 2024
BACKGROUND: Colorectal cancer is a public health issue and was the third leading cause of cancer-related death worldwide in 2022. Early diagnosis can improve prognosis, making screening a central part of colorectal cancer management. Blood-based screening, diagnosis and follow-up of colorectal cancer patients are possible with the study of cell-free circulating tumor DNA. This study aimed to identify novel DNA methylation biomarkers of colorectal cancer that can be used for the follow-up of patients with colorectal cancer. METHODS: A DNA methylation profile was established in the Gene Expression Omnibus (GEO) database (n = 507) using bioinformatics analysis and subsequently confirmed using The Cancer Genome Atlas (TCGA) database (n = 348). The in silico profile was then validated on local tissue and cell-free DNA samples using methylation-specific digital PCR in colorectal cancer patients (n = 35) and healthy donors (n = 35). RESULTS: The DNA methylation of COL25A1 and METAP1D was predicted to be a colorectal cancer biomarker by bioinformatics analysis (ROC AUC = 1, 95% CI [0.999-1]). The two biomarkers were confirmed with tissue samples, and the combination of COL25A1 and METAP1D yielded 49% sensitivity and 100% specificity for cell-free DNA. CONCLUSION: Bioinformatics analysis of public databases revealed COL25A1 and METAP1D DNA methylation as clinically applicable liquid biopsies DNA methylation biomarkers. The specificity implies an excellent positive predictive value for follow-up, and the high sensitivity and relative noninvasiveness of a blood-based test make these biomarkers compatible with colorectal cancer screening. However, the clinical impact of these biomarkers in colorectal cancer screening and follow-up needs to be established in further prospective studies.
2021
- Impact Factor < 5
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 screeningBMC Cancer, Oct 2021In 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. METHODS: Detection 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). 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™, this study shows that hypermethylation of NPY and WIF1 are constant specific biomarkers of CRCs regardless of a potential role in carcinogenesis.