MethCORR modelling of methylomes from formalin-fixed paraffin-embedded tissue enables characterization and prognostication of colorectal cancer.
Aged
Biomarkers, Tumor
/ genetics
Colon
/ pathology
Colorectal Neoplasms
/ genetics
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
Paraffin Embedding
Prognosis
Rectum
/ pathology
Risk Assessment
/ methods
Tissue Fixation
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
24 04 2020
24 04 2020
Historique:
received:
03
03
2019
accepted:
02
04
2020
entrez:
26
4
2020
pubmed:
26
4
2020
medline:
11
8
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32332866
doi: 10.1038/s41467-020-16000-6
pii: 10.1038/s41467-020-16000-6
pmc: PMC7181739
doi:
Substances chimiques
Biomarkers, Tumor
0
Formaldehyde
1HG84L3525
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2025Subventions
Organisme : NCI NIH HHS
ID : R01 CA207467
Pays : United States
Commentaires et corrections
Type : ErratumIn
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