{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Surgical & Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA",
    "Department of Biochemistry and Molecular Medicine, School of Medicine, University of California-Davis, Davis, CA 95817, USA",
    "Department of Pathology and Laboratory Medicine, School of Medicine, University of California-Davis, Davis, CA 95817, USA",
    "VA Northern California Health Care System, Sacramento, CA 95652, USA",
    "Department of Otolaryngology-Head and Neck Surgery, School of Medicine, University of California-Davis, Davis, CA 95817, USA",
    "Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Stephanie Goldschmidt",
      "orcid": "0000-0001-5944-4202"
    },
    {
      "affs": [
        1
      ],
      "name": "Clifford G. Tepper"
    },
    {
      "affs": [
        0
      ],
      "name": "Maria Soltero-Rivera",
      "orcid": "0000-0003-2272-3966"
    },
    {
      "affs": [
        0
      ],
      "name": "Rachel V. Brady",
      "orcid": "0000-0002-5688-3872"
    },
    {
      "affs": [
        2
      ],
      "name": "John Aleman",
      "orcid": "0000-0002-1691-6262"
    },
    {
      "affs": [
        0
      ],
      "name": "Robert Rebhun"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Xiao-Jing Wang"
    },
    {
      "affs": [
        4
      ],
      "name": "Andrew C. Birkeland"
    },
    {
      "affs": [
        2
      ],
      "name": "Karleen Meiklejohn"
    },
    {
      "affs": [
        0
      ],
      "name": "Ryan Todebusch"
    },
    {
      "affs": [
        5
      ],
      "name": "Clinson Lui"
    },
    {
      "affs": [
        5
      ],
      "name": "Brian G. Murphy",
      "orcid": "0000-0003-0057-0604"
    },
    {
      "affs": [
        5
      ],
      "name": "Natalia Vapniarsky",
      "orcid": "0000-0003-3239-6233"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3zxwndsqnnmp0.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27209163",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705180/?tool=EBI",
  "id": "3zxwndsqnnmp0",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/20/9163",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2740|Veterinary Oncology Research"
    ]
  ],
  "openalex": "W7221909494",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705180/pdf/?tool=EBI",
  "pmcid": "PMC13705180",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/3zxwndsqnnmp0.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:57Z",
      "native_id": "10.3390/ijms27209163",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/20/9163"
    },
    {
      "first_seen": "2026-10-30T12:21:31Z",
      "native_id": "PMC:PMC13705180",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13705180"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Veterinary Oncology Research",
      "subfield": "general"
    }
  ],
  "title": "Spatial Molecular Signatures of Canine Oral Squamous Cell Carcinoma with and Without Locoregional Metastasis with Cross-Species Comparison to Human Samples",
  "title_text": "Spatial Molecular Signatures of Canine Oral Squamous Cell Carcinoma with and Without Locoregional Metastasis with Cross-Species Comparison to Human Samples",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:31Z",
  "url": "https://research.draconitic.com/paper/3zxwndsqnnmp0",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}