MethCORR modelling of methylomes from formalin-fixed paraffin-embedded tissue enables characterization and prognostication of colorectal cancer

Trine B. Mattesen, Mads H. Rasmussen, Juan Sandoval, Halit Ongen, Sigrid S. Árnadóttir, Josephine Gladov, Anna Martinez-Cardus, Manuel Castro de Moura, Anders H. Madsen, Søren Laurberg, Emmanouil T. Dermitzakis, Manel Esteller, Claus L. Andersen*, Jesper B. Bramsen

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Abstract

Transcriptional characterization and classification has potential to resolve the inter-tumor heterogeneity of colorectal cancer and improve patient management. Yet, robust transcriptional profiling is difficult using formalin-fixed, paraffin-embedded (FFPE) samples, which complicates testing in clinical and archival material. We present MethCORR, an approach that allows uniform molecular characterization and classification of fresh-frozen and FFPE samples. MethCORR identifies genome-wide correlations between RNA expression and DNA methylation in fresh-frozen samples. This information is used to infer gene expression information in FFPE samples from their methylation profiles. MethCORR is here applied to methylation profiles from 877 fresh-frozen/FFPE samples and comparative analysis identifies the same two subtypes in four independent cohorts. Furthermore, subtype-specific prognostic biomarkers that better predicts relapse-free survival (HR = 2.66, 95%CI [1.67–4.22], P value < 0.001 (log-rank test)) than UICC tumor, node, metastasis (TNM) staging and microsatellite instability status are identified and validated using DNA methylation-specific PCR. The MethCORR approach is general, and may be similarly successful for other cancer types.

Original languageEnglish
Article number2025
JournalNature Communications
Volume11
ISSN2041-1723
DOIs
Publication statusPublished - Dec 2020

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