Spatial transcriptomic analysis of progressing oral epithelial dysplasia reveals unique differentially expressed genes and microenvironmental changes.

Authors

Vincent Lavoie, Erison Santana Dos Santos, Will Jeong, James S Jeon, Juan Fernandez Andrade, Aiman Ali, Graziella R Molska, Najmeh Esfandiari, Hui Ling Yeo, Igor Jurisica, Deepika Chugh, Iona Leong, Justin Bubola, Grace Bradley, Marco Magalhaes

Published in

Molecular cancer research : MCR. Sep 29, 2026. Epub Sep 29, 2026.

Abstract

Oral squamous cell carcinoma (OSCC) often arises from oral epithelial dysplasia (OED); however, the gene expression changes during OED progression and its microenvironment are not fully understood. This study used spatial transcriptomics to identify differentially expressed genes and microenvironmental alterations associated with malignant transformation of OED. A retrospective analysis of paired OSCC and OED samples was conducted at the Faculty of Dentistry, University of Toronto. A total of 24 paired progressing OED (OED-P) and 23 matched non-progressing OED (OED-NP) cases were examined using spatial transcriptomics in PanCK+ (epithelium) and PanCK- (stroma) regions. The analysis included differential gene expression, pathway analysis, and spatial deconvolution. Our results identified differentially expressed genes in OED-P compared with OED-NP and even more extensive changes between OED-P and matching OSCC. Pathway analysis supported the activation of immune pathways, ubiquitination, metabolic reprogramming, and matrix-remodeling signatures during progression. Functional validation shows that TNFRSF12A (Fn14) contributes to the molecular mechanisms underlying OED progression to OSCC. The OSCC microenvironment showed increased numbers of fibroblasts, neutrophils, monocytes, and mast cells compared with OED. We report a comprehensive transcriptional analysis of matched OED cases, and our results suggest that spatial profiling of OED can help identify unique and actionable gene signatures and microenvironmental changes that occur before oral malignant transformation. Implications: Our study identifies spatially resolved molecular alterations associated with oral cancer development and highlights Fn14 as a promising biomarker and therapeutic target for intercepting malignant transformation.

PMID:
42808889
Bibliographic data and abstract were imported from PubMed on 29 Sep 2026.

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