Integrative Clinical and DNA Methylation Analyses in a Population-Based Cohort Identifies and as Risk Recurrence Factors in Stage II Colon Cancer.

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Date publication

décembre 2022

Journal

Cancers

Auteurs

Membres identifiés du Cancéropôle Est :
Dr BOUVIER Anne-Marie, Dr CHAPUSOT Caroline, Pr GHIRINGHELLI François, Dr JOOSTE Valérie, Pr LEPAGE Côme, Pr MARTIN Laurent, Mme TRUNTZER Caroline, Pr MANFREDI Sylvain, Pr CALLANAN Mary, Dr AUCAGNE Romain


Tous les auteurs :
Tournier B, Aucagne R, Truntzer C, Fournier C, Ghiringhelli F, Chapusot C, Martin L, Bouvier AM, Manfredi S, Jooste V, Callanan MB, Lepage C

Résumé

Stage II colon cancer (CC), although diagnosed early, accounts for 16% of CC deaths. Predictors of recurrence risk could mitigate this but are currently lacking. By using a DNA methylation-based clinical screening in real-world ( = 383) and in TCGA-derived cohorts of stage II CC ( = 134), we have devised a novel 40 CpG site-based classifier that can segregate stage II CC into four previously undescribed disease sub-classes that are characterised by distinct molecular features, including activation of MYC/E2F-dependant proliferation signatures. By multivariate analyses, hypermethylation of 2 CpG sites at genes and , respectively, was found to independently confer either significantly increased (; -value, 0.0203) or reduced (; -value, 0.0047) risk of CC recurrence. Functional enrichment and immune cell infiltration analyses, on RNAseq data from the TCGA cohort, revealed cases with hypermethylation at to be enriched for , epithelial-mesenchymal transition and inflammatory functions (via IL2/STAT5), associated with infiltration by 'exhausted' T cells. By contrast, hypermethylated cases showed enrichment for mTORC1, DNA repair pathways and activated B cell signatures. These findings will be of value for improving personalised care paths and treatment in stage II CC patients.

Mots clés

LINE1, epigenetics, immune contexture, oncogene signalling, stage II colon cancer biomarkers, transforming growth factor beta (TGFβ)

Référence

Cancers (Basel). 2022 12 27;15(1):