Spatial transcriptomics reveals distinct and conserved tumor core and edge architectures that predict survival and targeted therapy response.
Nat Commun
; 14(1): 5029, 2023 08 18.
Article
em En
| MEDLINE
| ID: mdl-37596273
ABSTRACT
The spatial organization of the tumor microenvironment has a profound impact on biology and therapy response. Here, we perform an integrative single-cell and spatial transcriptomic analysis on HPV-negative oral squamous cell carcinoma (OSCC) to comprehensively characterize malignant cells in tumor core (TC) and leading edge (LE) transcriptional architectures. We show that the TC and LE are characterized by unique transcriptional profiles, neighboring cellular compositions, and ligand-receptor interactions. We demonstrate that the gene expression profile associated with the LE is conserved across different cancers while the TC is tissue specific, highlighting common mechanisms underlying tumor progression and invasion. Additionally, we find our LE gene signature is associated with worse clinical outcomes while TC gene signature is associated with improved prognosis across multiple cancer types. Finally, using an in silico modeling approach, we describe spatially-regulated patterns of cell development in OSCC that are predictably associated with drug response. Our work provides pan-cancer insights into TC and LE biology and interactive spatial atlases ( http//www.pboselab.ca/spatial_OSCC/ ; http//www.pboselab.ca/dynamo_OSCC/ ) that can be foundational for developing novel targeted therapies.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Bucais
/
Carcinoma de Células Escamosas
/
Neoplasias de Cabeça e Pescoço
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article