ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Increased Nerve Density Adversely Affects Outcome in Oral Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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32 citing papers in PubMed, 43 citations in OpenAlex.
- Neural regulation of cancer: from microenvironmental hijacking to systemic circuit co-option.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Association of tumor Schwann cells with epithelial-mesenchymal transition and immune-suppressive microenvironment in triple-negative breast cancer.Breast cancer research and treatment · 2026Article
- Transcriptome Analysis and Histological Validation Identified the HO-1-u-1 Cell Line as a Model for Perineural Invasion in Oral Squamous Cell Carcinoma.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2026Article
- Cancer-induced nerve injury unveils a sympathetic-to-sensory nerve axis in a mouse model of head and neck squamous cell carcinoma.Science translational medicine · 2026Article
- The suppressive function of ILC2 cells is regulated by β2-adrenergic receptor signaling in breast cancer.NPJ breast cancer · 2026Article
- Refining Postoperative Radiotherapy in Early-Stage Oral Squamous Cell Carcinoma: Impact of Perineural and Lymphovascular Invasion.Annals of surgical oncology · 2026Article
- Loss of salivary agglutinin induces changes in the salivary microbiome and accelerates development of oral cancer.Microbiome · 2026Article
- CGRP signaling links tumor-associated pain to immune evasion in oral squamous cell carcinoma.Cell reports · 2026Article
- Crosstalk of NPY and TGFβ orchestrates the signaling to facilitate perineural invasion of oral squamous cell carcinoma.British journal of cancer · 2026Article
- A hypothesis and evidence map for neuroimmune regulation of DOCK-family cytoskeletal programs in solid tumors.Frontiers in immunology · 2026Review
- CAV2-expressing nerves induce metabolic switch toward mitochondrial oxidative phosphorylation to promote cancer stemness.Nature communications · 2025Article
- Reprogramming neural-tumor crosstalk: emerging therapeutic dimensions and targeting strategies.Military Medical Research · 2025Review
- Turning cold tumors into hot tumors to ignite immunotherapy.Molecular cancer · 2025Review
- Tumor Innervation: From Bystander to Emerging Therapeutic Target for Cancer.International journal of molecular sciences · 2025Review
- Nerve Types and Classification of Neurons Innervating Oral Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Tumor innervation in cervical cancer: Prognostic insights from myelin-associated risk signatures.FASEB bioAdvances · 2025Article
- Cancer neuroscience in head and neck: interactions, modulation, and therapeutic strategies.Molecular cancer · 2025Review
- Increased nerve density adversely affects outcome in colorectal cancer and denervation suppresses tumor growth.Journal of translational medicine · 2025Article
- Tumor innervation and mitochondrial transfer in the cancer pathogenesis: perspectives on genitourinary malignancies.Frontiers in oncology · 2025Review
- Macrophage-derived cathepsin L promotes epithelial-mesenchymal transition and M2 polarization in gastric cancer.World journal of gastroenterology · 2024Article
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16 authors at 2 institutions in 1 country.
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Abstract
purposePerineural invasion (PNI) in oral cavity squamous cell carcinoma (OSCC) is associated with poor survival. Because of the risk of recurrence, patients with PNI receive additional therapies after surgical resection. Mechanistic studies have shown that nerves in the tumor microenvironment promote aggressive tumor growth. Therefore, in this study, we evaluated whether nerve density (ND) influences tumor growth and patient survival. Moreover, we assessed the reliability of artificial intelligence (AI) in evaluating ND. EXPERIMENTAL
designTo investigate whether increased ND in OSCC influences patient outcome, we performed survival analyses. Tissue sections of OSCC from 142 patients were stained with hematoxylin and eosin and IHC stains to detect nerves and tumor. ND within the tumor bulk and in the adjacent 2 mm was quantified; normalized ND (NND; bulk ND/adjacent ND) was calculated. The impact of ND on tumor growth was evaluated in chick chorioallantoic-dorsal root ganglia (CAM-DRG) and murine surgical denervation models. Cancer cells were grafted and tumor size quantified. Automated nerve detection, applying the Halo AI platform, was compared with manual assessment.
resultsDisease-specific survival decreased with higher intratumoral ND and NND in tongue SCC. Moreover, NND was associated with worst pattern-of-invasion and PNI. Increasing the number of DRG, in the CAM-DRG model, increased tumor size. Reduction of ND by denervation in a murine model decreased tumor growth. Automated and manual detection of nerves showed high concordance, with an F1 score of 0.977.
conclusionsHigh ND enhances tumor growth, and NND is an important prognostic factor that could influence treatment selection for aggressive OSCC. See related commentary by Hondermarck and Jiang, p. 2342.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.