Correlation between DNA Methylation and Cell Proliferation Identifies New Candidate Predictive Markers in Meningioma

Autor: Sébastien Hergalant, Chloé Saurel, Marion Divoux, Fabien Rech, Celso Pouget, Catherine Godfraind, Pierre Rouyer, Stéphanie Lacomme, Shyue-Fang Battaglia-Hsu, Guillaume Gauchotte
Přispěvatelé: Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), CHU Clermont-Ferrand, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), La Région Lorraine, Grand Est—projet de recherche d’intérêt régional 2016, INSERM U1256 NGERE.
Rok vydání: 2022
Předmět:
Zdroj: Cancers
Cancers, 2022, 14 (24), pp.6227. ⟨10.3390/cancers14246227⟩
Cancers; Volume 14; Issue 24; Pages: 6227
ISSN: 2072-6694
DOI: 10.3390/cancers14246227
Popis: International audience; Meningiomas are the most common primary tumors of the central nervous system. Based on the 2021 WHO classification, they are classified into three grades reflecting recurrence risk and aggressiveness. However, the WHO’s histopathological criteria defining these grades are somewhat subjective. Together with reliable immunohistochemical proliferation indices, other molecular markers such as those studied with genome-wide epigenetics promise to revamp the current prognostic classification. In this study, 48 meningiomas of various grades were randomly included and explored for DNA methylation with the Infinium MethylationEPIC microarray over 850k CpG sites. We conducted differential and correlative analyses on grade and several proliferation indices and markers, such as mitotic index and Ki-67 or MCM6 immunohistochemistry. We also set up Cox proportional hazard models for extensive associations between CpG methylation and survival. We identified loci highly correlated with cell growth and a targeted methylation signature of regulatory regions persistently associated with proliferation, grade, and survival. Candidate genes under the control of these regions include SMC4, ESRRG, PAX6, DOK7, VAV2, OTX1, and PCDHA-PCDHB-PCDHG, i.e., the protocadherin gene clusters. This study highlights the crucial role played by epigenetic mechanisms in shaping dysregulated cellular proliferation and provides potential biomarkers bearing prognostic and therapeutic value for the clinical management of meningioma.
Databáze: OpenAIRE
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