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.
- Type: Other
- Archiver: EGA European Genome-Phenome Archive
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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