ArticleJournal of translational medicine2024
The spatial distribution of intermediate fibroblasts and myeloid-derived cells dictate lymph node metastasis dynamics in oral cancer.
Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Spatial transcriptomics and artificial intelligence: a scoping review of emerging applications in head and neck pathology.Head and neck pathology · 2026Article
- Salivary Proteomic Signatures Reveal Novel Mechanistic Insights into Moderate Dental Fluorosis Pathogenesis and Oral Homeostasis Disruption.Computational and structural biotechnology journal · 2026Article
- Unraveling the impact of cancer-associated fibroblasts on lymphatic metastasis of head and neck squamous cell carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Integration of Single-cell and bulk RNA sequencing data uncovers lymphatic metastasis-related prognostic genes and a predictive model in bladder cancer.Scientific reports · 2025Article
- Recent advances in biomarker detection of oral squamous cell carcinoma.Frontiers in oncology · 2025Review
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Authors and funding
9 authors.
Funding
Abstract
backgroundOral cancer poses a significant health challenge due to limited treatment protocols and therapeutic targets. We aimed to investigate the invasive margins of gingivo-buccal oral squamous cell carcinoma (GB-OSCC) tumors in terms of the localization of genes and cell types within the margins at various distances that could lead to nodal metastasis.
methodsWe collected tumor tissues from 23 resected GB-OSCC samples for gene expression profiling using digital spatial transcriptomics. We monitored differential gene expression at varying distances between the tumor and its microenvironvent (TME), and performed a deconvulation study and immunohistochemistry to identify the cells and genes regulating the TME.
resultsWe found that the tumor-stromal interface (a distance up to 200 µm between tumor and immune cells) is the most active region for disease progression in GB-OSCC. The most differentially expressed apex genes, such as FN1 and COL5A1, were located at the stromal ends of the margins, and together with enrichment of the extracellular matrix (ECM) and an immune-suppressed microenvironment, were associated with lymph node metastasis. Intermediate fibroblasts, myocytes, and neutrophils were enriched at the tumor ends, while cancer-associated fibroblasts (CAFs) were enriched at the stromal ends. The intermediate fibroblasts transformed into CAFs and relocated to the adjacent stromal ends where they participated in FN1-mediated ECM modulation.
conclusionWe have generated a functional organization of the tumor-stromal interface in GB-OSCC and identified spatially located genes that contribute to nodal metastasis and disease progression. Our dataset might now be mined to discover suitable molecular targets in oral cancer.
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