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Integrated Multi-Omic Analysis of Epithelial and Stromal Changes during Progression of Barrett s Esophagus to Adenocarcinoma

ABSTRACT: Esophageal adenocarcinoma arises from Barrett s esophagus, the precancerous metaplastic replacement of squamous by columnar epithelium in response to chronic inflammation. Development of adenocarcinoma is accompanied by non-genetic plasticity of epithelial and stromal cells. Multiomics profiling, integrating single-cell transcriptomics, extracellular matrix proteomics, tissue mechanics and spatial multiplexed proteomics of 64 samples from 12 patient trajectories of progression from normal epithelium, to metaplasia, dysplasia and adenocarcinoma, revealed shared and patient-specific progression paths. We detected profound consistent alterations of type and composition of tumor microenvironment cells, matrix composition and cell neighborhoods. Stromal cells with characteristics of cancer-associated fibroblasts appear early at the premalignant metaplastic stage. Thus, Barrett s esophagus progresses as a coordinated multi-component system, supporting a treatment paradigm that incorporates tissue reprogramming beyond targeting cancerous cells.

INSTRUMENT(S): TripleTOF 6600

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Birgit Schilling

PROVIDER: MSV000091366 | MassIVE | Sat Feb 25 20:01:00 GMT 2023

SECONDARY ACCESSION(S): PXD040397

REPOSITORIES: MassIVE

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