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

Nat Commun. 2020 Apr 24;11(1):2025. doi: 10.1038/s41467-020-16000-6.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics*
  • Colon / pathology
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality*
  • Colorectal Neoplasms / pathology
  • DNA Methylation
  • Datasets as Topic
  • Disease-Free Survival
  • Epigenome / genetics*
  • Female
  • Formaldehyde
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intestinal Mucosa / pathology
  • Male
  • Middle Aged
  • Models, Genetic*
  • Neoplasm Recurrence, Local / diagnosis*
  • Neoplasm Recurrence, Local / genetics
  • Paraffin Embedding
  • Prognosis
  • Rectum / pathology
  • Risk Assessment / methods
  • Tissue Fixation

Substances

  • Biomarkers, Tumor
  • Formaldehyde