ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
Spatial and Transcriptomic Analysis of Perineural Invasion in Oral Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 77 citations in OpenAlex.
- Clinical Impact of Rapid Recurrence in Oral Tongue Squamous Cell Carcinoma and a Nomogram for Early Identification of High-Risk Patients.Clinical and experimental otorhinolaryngology · 2026Article
- Understanding nerve-tumor interactions: From basic biology to therapeutic innovation.Genes & diseases · 2026Review
- Refining Postoperative Radiotherapy in Early-Stage Oral Squamous Cell Carcinoma: Impact of Perineural and Lymphovascular Invasion.Annals of surgical oncology · 2026Article
- Extracellular Vesicle-Mediated O-GlcNAcase Transfer Drives Neuronal Necroptosis to Facilitate Gallbladder Cancer Perineural Invasion.Cancer research · 2026Article
- Crosstalk of NPY and TGFβ orchestrates the signaling to facilitate perineural invasion of oral squamous cell carcinoma.British journal of cancer · 2026Article
- Histology and immune impact in OSCC.Brazilian dental journal · 2026Article
- CAV2-expressing nerves induce metabolic switch toward mitochondrial oxidative phosphorylation to promote cancer stemness.Nature communications · 2025Article
- Perineural Invasion Exhibits Traits of Neurodegeneration.Journal of dental research · 2025Article
- Reprogramming neural-tumor crosstalk: emerging therapeutic dimensions and targeting strategies.Military Medical Research · 2025Review
- Tumor Innervation: From Bystander to Emerging Therapeutic Target for Cancer.International journal of molecular sciences · 2025Review
- Cancer and neurotransmitter receptors.Chinese medical journal · 2025Review
- MAGEA6 Engages a YY1-Dependent Transcription to Dictate Perineural Invasion in Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- 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
- β-blocker suppresses both tumoral sympathetic neurons and perivascular macrophages during oncolytic herpes virotherapy.Journal for immunotherapy of cancer · 2025Article
- Cancer neuroscience in head and neck: interactions, modulation, and therapeutic strategies.Molecular cancer · 2025Review
- Quantifying and interpreting biologically meaningful spatial signatures within tumor microenvironments.NPJ precision oncology · 2025Review
- Unveiling a novel cancer hallmark by evaluation of neural infiltration in cancer.Briefings in bioinformatics · 2025Article
- Spatial Transcriptomics Reveals Novel Mechanisms Involved in Perineural Invasion in Pancreatic Ductal Adenocarcinomas.Cancers · 2025Article
- Nerves at Play: The Peripheral Nervous System in Extracranial Malignancies.Cancer discovery · 2025Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
purposePerineural invasion (PNI), a common occurrence in oral squamous cell carcinomas, is associated with poor survival. Consequently, these tumors are treated aggressively. However, diagnostic criteria of PNI vary and its role as an independent predictor of prognosis has not been established. To address these knowledge gaps, we investigated spatial and transcriptomic profiles of PNI-positive and PNI-negative nerves. EXPERIMENTAL
designTissue sections from 142 patients were stained with S100 and cytokeratin antibodies. Nerves were identified in two distinct areas: tumor bulk and margin. Nerve diameter and nerve-to-tumor distance were assessed; survival analyses were performed. Spatial transcriptomic analysis of nerves at varying distances from tumor was performed with NanoString GeoMx Digital Spatial Profiler Transcriptomic Atlas.
resultsPNI is an independent predictor of poor prognosis among patients with metastasis-free lymph nodes. Patients with close nerve-tumor distance have poor outcomes even if diagnosed as PNI negative using current criteria. Patients with large nerve(s) in the tumor bulk survive poorly, suggesting that even PNI-negative nerves facilitate tumor progression. Diagnostic criteria were supported by spatial transcriptomic analyses of >18,000 genes; nerves in proximity to cancer exhibit stress and growth response changes that diminish with increasing nerve-tumor distance. These findings were validated in vitro and in human tissue.
conclusionsThis is the first study in human cancer with high-throughput gene expression analysis in nerves with striking correlations between transcriptomic profile and clinical outcomes. Our work illuminates nerve-cancer interactions suggesting that cancer-induced injury modulates neuritogenesis, and supports reclassification of PNI based on nerve-tumor distance rather than current subjective criteria.
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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.