Journal article
Pathogenomic Fingerprinting to Identify Associations Between Tumor Morphology and Epigenetic States
European journal of cancer (1990), Vol.221, 115429
05/15/2025
DOI: 10.1016/j.ejca.2025.115429
PMCID: PMC12042128
PMID: 40239399
Abstract
Measuring the chromatin state of a tumor provides a powerful map of its epigenetic commitments; however, as these are generally bulk measurements, it has not yet been possible to connect changes in chromatin accessibility to the pathological signatures of complex tumors. In parallel, recent advances in computational pathology have enabled the identification of spatial features and immune cells within oral cavity tumors and their microenvironment.
Here, we present pathogenomic fingerprinting (PaGeFin), a novel method that integrates morphological tumor features with chromatin states using ATAC-seq. This framework links spatial morphologic and epigenetic features, offering insights into tumor progression and immune evasion within and across tumors. Morphologic features describing spatial relationships between tumor and lymphocyte cells that are prognostic of oral cavity squamous cell carcinoma (OSCC) were identified through AI-driven pathology analysis. These pathomic features were spatially colocalized within the epigenome of 4 distinct sections of 4 OSCC tumors.
These key features pinpointed chromatin regions responsible for critical immune cell function through peak locations and enrichment analysis, highlighting loci of CD27+ memory B cells, helper CD4+ T cells, and cytotoxic CD8 naïve T cells that likely drive morphologic changes in the distribution of lymphocytes in the tumor microenvironment and promote aggressive tumor behavior. Gene Ontology analysis revealed that the CTLA4, CD79A, CD3D, and CCR7 genes were embedded in these regions.
This computational approach is the first to assess the correlation between pathomic and epigenetic features in the context of cancer.
•PaGeFin uses ATAC-seq to link spatial and epigenetic tumor features.•AI-driven pathology analysis identifies prognostic immune features in OSCC•Chromatin accessibility mapping to immune loci associated with tumor progression•First framework to characterize tumor heterogeneity in OSCC at the cell level
Details
- Title: Subtitle
- Pathogenomic Fingerprinting to Identify Associations Between Tumor Morphology and Epigenetic States
- Creators
- Shayan Monabbati - Case Western Reserve UniversityGermán Corredor - Emory University School of MedicineTilak Pathak - Emory University School of MedicineCraig Peacock - Case Western Reserve UniversityKailin Yang - University of Iowa Holden Comprehensive Cancer CenterShlomo Koyfman - Cleveland ClinicPeter Scacheri - Case Western Reserve UniversityJames Lewis - Mayo Clinic in ArizonaAnant Madabhushi - Emory University School of MedicineSatish E. Viswanath - Case Western Reserve UniversityBerkley Gryder - Case Western Reserve University
- Resource Type
- Journal article
- Publication Details
- European journal of cancer (1990), Vol.221, 115429
- DOI
- 10.1016/j.ejca.2025.115429
- PMID
- 40239399
- PMCID
- PMC12042128
- NLM abbreviation
- Eur J Cancer
- ISSN
- 0959-8049
- eISSN
- 1879-0852
- Publisher
- Elsevier Ltd
- Grant note
- Congressionally Directed Medical Research Program: W81XWH 19-1-0668
This work was primarily supported by a generous donation from the Novick Family as well as the Congressionally Directed Medical Research Program (W81XWH 19-1-0668) . This work made use of the High-Performance Computing Resource in the Core Facility for Advanced Research Computing at Case Western Reserve University. The content is solely the responsibility of the authors and does not necessarily repre-sent the official views of the National Institutes of Health, the U.S. Department of Veterans Affairs, the Department of Defense, or the United States Government.
- Language
- English
- Electronic publication date
- 04/14/2025
- Date published
- 05/15/2025
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984810950802771
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