Cancer-associated fibroblasts reveal aberrant DNA methylation across different types of cancer.

Autor: Schmidt M; Institute for Stem Cell Biology, RWTH Aachen University Medical School, 52074, Aachen, Germany.; Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University Medical School, 52074, Aachen, Germany., Maié T; Institute for Computational Genomics, Joint Research Center for Computational Biomedicine, RWTH Aachen University Medical School, 52074, Aachen, Germany., Cramer T; Department of General, Visceral, Children and Transplantation Surgery, RWTH Aachen University Hospital, 52074, Aachen, Germany., Costa IG; Institute for Computational Genomics, Joint Research Center for Computational Biomedicine, RWTH Aachen University Medical School, 52074, Aachen, Germany., Wagner W; Institute for Stem Cell Biology, RWTH Aachen University Medical School, 52074, Aachen, Germany. wwagner@ukaachen.de.; Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University Medical School, 52074, Aachen, Germany. wwagner@ukaachen.de.; Center for Integrated Oncology, Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, Germany. wwagner@ukaachen.de.
Jazyk: angličtina
Zdroj: Clinical epigenetics [Clin Epigenetics] 2024 Nov 20; Vol. 16 (1), pp. 164. Date of Electronic Publication: 2024 Nov 20.
DOI: 10.1186/s13148-024-01783-y
Abstrakt: Background: Cancer-associated fibroblasts (CAFs) are essential components of the tumor microenvironment and play a critical role in cancer progression. Numerous studies have identified significant molecular differences between CAFs and normal tissue-associated fibroblasts (NAFs). In this study, we isolated CAFs and NAFs from liver tumors and conducted a comprehensive analysis of their DNA methylation profiles, integrating our finding with data from studies on other cancer types.
Results: Our analysis revealed that several CAF samples exhibited aberrant DNA methylation patterns, which corresponded with altered gene expression levels. Notably, DNA methylation at liver CAF-specific CpG sites was linked to survival outcomes in liver cancer datasets. An integrative analysis using publicly available datasets from various cancer types, including lung, prostate, esophageal, and gastric cancers, uncovered common epigenetic abnormalities across these cancers. Among the consistently altered CpGs were cg09809672 (EDARADD), cg07134930 (HDAC4), and cg05935904 (intergenic). These methylation changes were associated with prognosis across multiple cancer types.
Conclusion: The activation of CAFs by the tumor microenvironment seems to be associated with distinct epigenetic modifications. Remarkably, similar genomic regions tend to undergo hypomethylation in CAFs across different studies and cancer types. Our findings suggest that CAF-associated DNA methylation changes hold potential as prognostic biomarkers. However, further research and validation are necessary to develop and apply such signatures in a clinical setting.
Competing Interests: Declarations. Ethics approval and consent to participate: Liver biopsies were received from the Clinic for General, Visceral, Children and Transplantation Surgery at the University Hospital of RWTH Aachen after informed and written consent and following the guidelines of the Ethic Committee for the Use of Human Subjects at the University of Aachen (Permit number: EK 206/09). Consent for publication: Not applicable. Availability of data and materials: DNA methylation profiles generated in this study can be accessed from the Gene expression omnibus (GEO) under accession number GSE255123; the RNA-sequencing data are accessible under GSE255122. The following tokens have been created to allow review of the records GSE255123 (qxahsaionterlqr) and GSE255122 (khmjmegabnmjnqn). Competing interests: W.W. is involved in the company Cygenia GmbH ( www.cygenia.com ) that can provide service for epigenetic analysis to other scientists. Apart from this, the authors have no competing interests to declare.
(© 2024. The Author(s).)
Databáze: MEDLINE
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