Validation of hypermethylated DNA regions found in colorectal cancers as potential aging-independent biomarkers of precancerous colorectal lesions.

Autor: Sajibu S; Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland., Sonder E; Department of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, Zurich, 8057, Switzerland.; Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland., Tiwari A; Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland., Orjuela S; Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland., Parker HR; Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland., Frans OT; Division of Gastroenterology, Triemli Hospital, Zurich, Switzerland., Gubler C; Division of Gastroenterology, Triemli Hospital, Zurich, Switzerland., Marra G; Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland., Robinson MD; Department of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, Zurich, 8057, Switzerland. mark.robinson@mls.uzh.ch.; SIB Swiss Institute of Bioinformatics, Vaud, Switzerland. mark.robinson@mls.uzh.ch.
Jazyk: angličtina
Zdroj: BMC cancer [BMC Cancer] 2023 Oct 18; Vol. 23 (1), pp. 998. Date of Electronic Publication: 2023 Oct 18.
DOI: 10.1186/s12885-023-11487-w
Abstrakt: Background: We previously identified 16,772 colorectal cancer-associated hypermethylated DNA regions that were also detectable in precancerous colorectal lesions (preCRCs) and unrelated to normal mucosal aging. We have now conducted a study to validate 990 of these differentially methylated DNA regions (DMRs) in a new series of preCRCs.
Methods: We used targeted bisulfite sequencing to validate these 990 potential biomarkers in 59 preCRC tissue samples (41 conventional adenomas, 18 sessile serrated lesions), each with a patient-matched normal mucosal sample. Based on differential DNA methylation tests, a panel of candidate DMRs was chosen on a subset of our cohort and then validated on the remaining part of our cohort and two publicly available datasets with respect to their stratifying potential between preCRCs and normal mucosa.
Results: Strong statistical significance for the difference in methylation levels was observed across the full set of 990 investigated DMRs. From these, a selected candidate panel of 30 DMRs correctly identified 58/59 tumors (area under the receiver operating curve: 0.998).
Conclusions: These validated DNA hypermethylation markers can be exploited to develop more accurate noninvasive colorectal tumor screening assays.
(© 2023. BioMed Central Ltd., part of Springer Nature.)
Databáze: MEDLINE
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