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MethCORR Modelling of Methylomes From Formalin-Fixed Paraffin-Embedded Tissue Enables Characterization and Prognostication of Colorectal Cancer

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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.

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Nature Communications, 2020, vol. 11, num. 2025

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cc-by (c) Mattesen, Trine B. et al., 2020

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Articles publicats en revistes (Ciències Fisiològiques)

# metadata.dc.title[].value
MethCORR Modelling of Methylomes From Formalin-Fixed Paraffin-Embedded Tissue Enables Characterization and Prognostication of Colorectal Cancer