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Multi‐omics analyses reveal spatial heterogeneity in primary and metastatic oesophageal squamous cell carcinoma
- Source :
- Clinical and Translational Medicine, Vol 13, Iss 11, Pp n/a-n/a (2023)
- Publication Year :
- 2023
- Publisher :
- Wiley, 2023.
-
Abstract
- Abstract Background Biopsies obtained from primary oesophageal squamous cell carcinoma (ESCC) guide diagnosis and treatment. However, spatial intra‐tumoral heterogeneity (ITH) influences biopsy‐derived information and patient responsiveness to therapy. Here, we aimed to elucidate the spatial ITH of ESCC and matched lymph node metastasis (LNmet). Methods Primary tumour superficial (PTsup), deep (PTdeep) and LNmet subregions of patients with locally advanced resectable ESCC were evaluated using whole‐exome sequencing (WES), whole‐transcriptome sequencing and spatially resolved digital spatial profiling (DSP). To validate the findings, immunohistochemistry was conducted and a single‐cell transcriptomic dataset was analysed. Results WES revealed 15.72%, 5.02% and 32.00% unique mutations in PTsup, PTdeep and LNmet, respectively. Copy number alterations and phylogenetic trees showed spatial ITH among subregions both within and among patients. Driver mutations had a mixed intra‐tumoral clonal status among subregions. Transcriptome data showed distinct differentially expressed genes among subregions. LNmet exhibited elevated expression of immunomodulatory genes and enriched immune cells, particularly when compared with PTsup (all P
Details
- Language :
- English
- ISSN :
- 20011326
- Volume :
- 13
- Issue :
- 11
- Database :
- Directory of Open Access Journals
- Journal :
- Clinical and Translational Medicine
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.1453d8813e374a2f9260060233cc5e30
- Document Type :
- article
- Full Text :
- https://doi.org/10.1002/ctm2.1493