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

Fecha de publicación: Fecha Ahead of Print:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Mattesen, TB
  • Rasmussen, MH
  • Ongen, H
  • Arnadottir, SS
  • Gladov, J
  • Martinez-Cardus, A
  • Castro de Moura, M
  • Madsen, AH
  • Laurberg, S
  • Dermitzakis, ET
  • Esteller, M
  • Andersen, CL
  • Bramsen, JB

Grupos

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], Pvalue <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.

Datos de la publicación

ISSN/ISSNe:
2041-1723, 2041-1723

Nature Communications  NATURE PORTFOLIO

Tipo:
Article
Páginas:
2025-2025
PubMed:
32332866
Factor de Impacto:
5,559 SCImago ℠
Cuartil:
Q1 SCImago ℠

Citas Recibidas en Web of Science: 7

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Keywords

  • SET ENRICHMENT ANALYSIS; DNA METHYLATION; VALIDATION; PREDICTION; PROGNOSIS; SIGNATURE; CARCINOMA

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