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MethCORR: DNA Methylation-based Characterization, Classification and Prognostication of Colorectal Cancer using Archival Formalin-fixed, Paraffin-embedded Tissue

Transcriptional characterization and classification has potential to resolve the inter-tumor heterogeneity of colorectal cancer (CRC) 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 DNA methylation profiles. MethCORR was applied to methylation profiles from 877 fresh-frozen and FFPE samples and comparative analysis identified the same two major subtypes in four independent cohorts. Furthermore, subtype-specific prognostic biomarkers that better predicted relapse-free survival (HR=2.66, 95% CI [1.67-4.22], P<0.001) than TNM staging and MSI status were identified and validated using DNA methylation-specific PCR assays. The MethCORR approach is general, and may be similarly successful for other cancer types.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00010001888 Illumina 450k 314
Publications Citations
MethCORR modelling of methylomes from formalin-fixed paraffin-embedded tissue enables characterization and prognostication of colorectal cancer.
Nat Commun 11: 2020 2025
MSIMEP: Predicting microsatellite instability from microarray DNA methylation tumor profiles.
iScience 26: 2023 106127