[en] [en] 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.
Disciplines :
Oncology
Author, co-author :
Overs, Alexis; Department of Oncobiology, University Hospital of Besançon, 3 Boulevard Alexandre Fleming, 25000, Besançon, France. aovers@chu-besancon.fr ; UMR1098, INSERM, University of Bourgogne Franche-Comté, Besançon, France. aovers@chu-besancon.fr
Peixoto, Paul; UMR1098, INSERM, University of Bourgogne Franche-Comté, Besançon, France
Hervouet, Eric; UMR1098, INSERM, University of Bourgogne Franche-Comté, Besançon, France
Molimard, Chloé; Department of Pathology, University Hospital of Besançon, 25000, Besancon, France
Monnien, Franck; Department of Pathology, University Hospital of Besançon, 25000, Besancon, France
Durand, Jules; UMR1098, INSERM, University of Bourgogne Franche-Comté, Besançon, France
Guittaut, Michael; UMR1098, INSERM, University of Bourgogne Franche-Comté, Besançon, France
Vienot, Angélique; Department of Oncology, University Hospital of Besançon, 25000, Besancon, France
Viot, Julien; Department of Oncology, University Hospital of Besançon, 25000, Besancon, France
Herfs, Michael ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Borg, Christophe; UMR1098, INSERM, University of Bourgogne Franche-Comté, Besançon, France ; Department of Oncology, University Hospital of Besançon, 25000, Besancon, France
Feugeas, Jean-Paul; Department of Oncobiology, University Hospital of Besançon, 3 Boulevard Alexandre Fleming, 25000, Besançon, France ; UMR1098, INSERM, University of Bourgogne Franche-Comté, Besançon, France
Selmani, Zohair; Department of Oncobiology, University Hospital of Besançon, 3 Boulevard Alexandre Fleming, 25000, Besançon, France ; UMR1098, INSERM, University of Bourgogne Franche-Comté, Besançon, France
We thank all the patients and donors who agreed to participate in this study. We thank the EPIgenetics and GENe EXPression Technical Platform (EPIGENExp) for making the Bio-Rad digital PCR device available, their expertise for the design of the experiments, and their help for the results analysis. This study was also supported by CELIA grant of Besan\u00E7on university hospital.
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