Supplementary Table S5 from Nerve Types and Classification of Neurons Innervating Oral Cancer

Perez-Pacheco, Cindy G.; Gonzalez-Maldonado, Laura A.; Furgal, Allison; Schmitd, Ligia B.; Constantinescu, Brian S.C.; Li, Yihan; Gannot, Noam; Perry, Sienna K.; Rozek, Laura; Wolf, Greg; Emrick, Joshua J.; Li, Peng; D’Silva, Nisha J.

doi:10.1158/1078-0432.29444873

Supplementary Table S5 from Nerve Types and Classification of Neurons Innervating Oral Cancer

journal contribution

posted on 2025-07-01, 07:24 authored by Cindy G. Perez-Pacheco, Laura A. Gonzalez-Maldonado, Allison Furgal, Ligia B. Schmitd, Brian S.C. Constantinescu, Yihan Li, Noam Gannot, Sienna K. Perry, Laura Rozek, Greg Wolf, Joshua J. Emrick, Peng Li, Nisha J. D’Silva

<p>Distribution of nerve types in tumor margin by tumor stage (AJCC 8th ed) in 48 patients with tongue tumors.</p>

Funding

National Institute of Dental and Craniofacial Research (NIDR)

School of Dentistry, University of Michigan (U-M School of Dentistry)

History

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1.
DOI - Is supplement to Nerve Types and Classification of Neurons Innervating Oral Cancer

ARTICLE ABSTRACT

Although the association between neural invasion and poor survival in oral cavity squamous cell carcinoma (OSCC) is known, innervating nerve types have not been definitively established; this has confounded mechanistic and translational studies. Therefore, we investigated innervation in human OSCC and further explored these findings in mice. Sensory, sympathetic, and parasympathetic nerves were identified by IHC and linked to neural phenotypes in 71 patients. Additionally, we investigated sensory innervation of OSCC using neuronal tracing with transcriptomic profiling in transgenic mice. In OSCC, most nerves are exclusively sensory or sensory mixed with other types. The presence of exclusively sensory nerves and mixed sensory and sympathetic nerves was significantly increased within the tumor bulk compared with the margin, whereas mixed sympathetic and parasympathetic nerves were decreased. The proportion of exclusively sensory and mixed sensory and sympathetic perineural invasion–positive nerves was significantly higher, whereas the proportion of mixed sympathetic and parasympathetic nerves was significantly lower than that of perineural invasion–negative nerves. Classification of tumor-innervating trigeminal sensory neurons in mice revealed an increase in Calca+ peptidergic nociceptors and reduction in low-threshold mechanoreceptors. Using transgenic reporter mice to verify innervation, we identified that mouse tongue SCC is innervated by Pirt+ and Calca+ nociceptors. This study is the first comprehensive characterization of nerve types in OSCC with classification of innervating trigeminal sensory neurons. Our findings emphasize the importance of sensory innervation in OSCC and are highly relevant for mechanistic and translational studies on treatment strategies.