Spatial Molecular Signatures of Canine Oral Squamous Cell Carcinoma with and Without Locoregional Metastasis with Cross-Species Comparison to Human Samples
6 affiliations
- 1Department of Surgical & Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA
- 2Department of Biochemistry and Molecular Medicine, School of Medicine, University of California-Davis, Davis, CA 95817, USA
- 3Department of Pathology and Laboratory Medicine, School of Medicine, University of California-Davis, Davis, CA 95817, USA
- 4VA Northern California Health Care System, Sacramento, CA 95652, USA
- 5Department of Otolaryngology-Head and Neck Surgery, School of Medicine, University of California-Davis, Davis, CA 95817, USA
- 6Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA
Abstract
Accurate diagnosis of locoregional spread in head and neck squamous cell carcinoma (HNSCC) is critical for prognosis and treatment planning. However, the currently available pre-surgical staging modalities often fail to detect occult nodal metastasis, necessitating nodal extirpation for accurate pathologic staging. This approach carries no clinical benefit and introduces unwarranted morbidity in patients with nonmetastatic lymph nodes (pN0 neck). The aim of this study was to define the molecular landscape of HNSCC in a spontaneous model of disease (pet dogs) with and without pathologically confirmed locoregional metastasis to identify biomarkers that may improve risk stratification and guide nodal management. Spatial transcriptomic profiling revealed a distinct metastatic tumor signature characterized by downregulation of PTEN, EPSTI1, CD99, MAPKAPK2, OAZ1, and upregulation of LOC477699. The tumor microenvironment of metastatic tumors demonstrated reduced JAK1 and trends consistent with T-cell exhaustion. Metastatic lymph node deposits conserved transcriptomic signatures matched to the primary tumor, and peri-metastatic lymph nodes displayed potentially permissive molecular alterations, including reduced F13A1 and DLA88 expression. Cross-species comparisons with human datasets identified conserved molecular and pathway-level features. Collectively, these findings identify candidate biomarkers and biological pathways associated with locoregional metastasis and support future prospective validation in canine and human HNSCC.
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BibTeX
@article{goldschmidt2026spatial,
title = {{Spatial Molecular Signatures of Canine Oral Squamous Cell Carcinoma with and Without Locoregional Metastasis with Cross-Species Comparison to Human Samples}},
author = {Stephanie Goldschmidt and Clifford G. Tepper and Maria Soltero-Rivera and Rachel V. Brady and John Aleman and Robert Rebhun and Xiao-Jing Wang and Andrew C. Birkeland and Karleen Meiklejohn and Ryan Todebusch and Clinson Lui and Brian G. Murphy and Natalia Vapniarsky},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209163},
url = {https://www.mdpi.com/1422-0067/27/20/9163},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Spatial Molecular Signatures of Canine Oral Squamous Cell Carcinoma with and Without Locoregional Metastasis with Cross-Species Comparison to Human Samples
AU - Stephanie Goldschmidt
AU - Clifford G. Tepper
AU - Maria Soltero-Rivera
AU - Rachel V. Brady
AU - John Aleman
AU - Robert Rebhun
AU - Xiao-Jing Wang
AU - Andrew C. Birkeland
AU - Karleen Meiklejohn
AU - Ryan Todebusch
AU - Clinson Lui
AU - Brian G. Murphy
AU - Natalia Vapniarsky
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209163
UR - https://www.mdpi.com/1422-0067/27/20/9163
AB - Accurate diagnosis of locoregional spread in head and neck squamous cell carcinoma (HNSCC) is critical for prognosis and treatment planning. However, the currently available pre-surgical staging modalities often fail to detect occult nodal metastasis, necessitating nodal extirpation for accurate pathologic staging. This approach carries no clinical benefit and introduces unwarranted morbidity in patients with nonmetastatic lymph nodes (pN0 neck). The aim of this study was to define the molecular landscape of HNSCC in a spontaneous model of disease (pet dogs) with and without pathologically confirmed locoregional metastasis to identify biomarkers that may improve risk stratification and guide nodal management. Spatial transcriptomic profiling revealed a distinct metastatic tumor signature characterized by downregulation of PTEN, EPSTI1, CD99, MAPKAPK2, OAZ1, and upregulation of LOC477699. The tumor microenvironment of metastatic tumors demonstrated reduced JAK1 and trends consistent with T-cell exhaustion. Metastatic lymph node deposits conserved transcriptomic signatures matched to the primary tumor, and peri-metastatic lymph nodes displayed potentially permissive molecular alterations, including reduced F13A1 and DLA88 expression. Cross-species comparisons with human datasets identified conserved molecular and pathway-level features. Collectively, these findings identify candidate biomarkers and biological pathways associated with locoregional metastasis and support future prospective validation in canine and human HNSCC.
SN - 1422-0067
ER -