Spatial transcriptomics reveals distinct and conserved tumor core and edge architectures that predict survival and targeted therapy response

Rohit Arora, Christian Cao, Mehul Kumar, Sarthak Sinha, Ayan Chanda, Reid McNeil, Divya Samuel, Rahul K. Arora, T. Wayne Matthews, Shamir Chandarana, Robert Hart, Joseph C. Dort, Jeff Biernaskie, Paola Neri, Martin D. Hyrcza and Pinaki Bose ()
Additional contact information
Rohit Arora: University of Calgary
Christian Cao: University of Calgary
Mehul Kumar: University of Calgary
Sarthak Sinha: University of Calgary
Ayan Chanda: University of Calgary
Reid McNeil: University of Calgary
Divya Samuel: University of Calgary
Rahul K. Arora: University of Calgary
T. Wayne Matthews: University of Calgary
Shamir Chandarana: University of Calgary
Robert Hart: University of Calgary
Joseph C. Dort: University of Calgary
Jeff Biernaskie: University of Calgary
Paola Neri: University of Calgary
Martin D. Hyrcza: University of Calgary
Pinaki Bose: University of Calgary

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41467-023-40271-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40271-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-40271-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().