ArticleCancer science2019
Reduction of intrapancreatic neural density in cancer tissue predicts poorer outcome in pancreatic ductal carcinoma.
Article in Cancer science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 42 citations in OpenAlex.
- Decoding neuro-tumor interactions in pancreatic cancer: mechanisms, immunosuppressive networks and therapeutic opportunities.Molecular biomedicine · 2026Review
- Remodeling the tumor dormancy ecosystem to prevent recurrence and metastasis.Signal transduction and targeted therapy · 2026Review
- Sphingolipid metabolic enzyme GLA expression in gliomas: prognostic implications and therapeutic potential.Frontiers in oncology · 2026Article
- Reprogramming neural-tumor crosstalk: emerging therapeutic dimensions and targeting strategies.Military Medical Research · 2025Review
- Neuroimmune Interactions in Pancreatic Cancer.Biomedicines · 2025Review
- Increased nerve density adversely affects outcome in colorectal cancer and denervation suppresses tumor growth.Journal of translational medicine · 2025Article
- The supporting role of Schwann cells in perineural invasion of pancreatic ductal adenocarcinoma.Frontiers in pharmacology · 2025Review
- Endosomal Trafficking Bypassed by the RAB5B-CD109 Interplay Promotes Axonogenesis in KRAS-Mutant Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Remarks on Selected Morphological Aspects of Cancer Neuroscience: A Microscopic Photo Review.Biomedicines · 2024Review
- Targeting the peripheral neural-tumour microenvironment for cancer therapy.Nature reviews. Drug discovery · 2024Review
- Periampullary cancer and neurological interactions: current understanding and future research directions.Frontiers in oncology · 2024Review
- Crosstalk Between Peripheral Innervation and Pancreatic Ductal Adenocarcinoma.Neuroscience bulletin · 2023Review
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- Article
- Pancreatic Ductal Adenocarcinoma Induces Neural Injury that Promotes a Transcriptomic and Functional Repair Signature by Peripheral Neuroglia.Research square · 2023Article
- Prognostic analysis of curatively resected pancreatic cancer using harmonized positron emission tomography radiomic features.European journal of hybrid imaging · 2023Article
- Review
- Peak density of immature nerve cells occurs with high-grade dysplasia in intraductal papillary mucinous neoplasms of the pancreas.The Journal of pathology · 2022Article
- Current Pathology Model of Pancreatic Cancer.Cancers · 2022Review
- Limitations of Nerve Fiber Density as a Prognostic Marker in Predicting Oncological Outcomes in Hepatocellular Carcinoma.Cancers · 2022Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Neural invasion is one of the malignant features contributing to locally advanced and/or metastatic disease progression in patients with pancreatic ductal adenocarcinoma (PDAC). Few studies exist on the distribution and state of nerve fibers in PDAC tissue and their clinicopathological impacts. The aim of the present study was to investigate the clinicopathological characteristics and prognostic value of intrapancreatic neural alterations in patients with PDAC. We retrospectively analyzed 256 patients with PDAC who underwent macroscopic curative surgery. Nerve fibers, immunolabeled with a specific neural marker GAP-43, were digitally counted and compared among PDAC, chronic pancreatitis (CP) and normal pancreatic tissues. Interlobular nerve fibers were apparently hypertrophic in both CP and PDAC, although intrapancreatic neural density and nerve number decreased characteristically in PDAC. They tended to decrease toward the center of the tumor. Kaplan-Meier survival analyses revealed a statistically significant correlation between low neural density and shorter overall survival (OS) (P = 0.014), and between high neural invasion and shorter OS (P = 0.017). Neural density (P = 0.04; HR = 1.496; 95% CI 1.018-2.199) and neural invasion ratio (P = 0.064; HR = 1.439; 95% CI .980-2.114) were prognostic factors of shorter OS in the multivariate analysis. These findings suggest low intrapancreatic neural density in patients with PDAC as an independent prognosticator, which may represent aggressive tumor behavior. Furthermore, we propose a simple, practical and reproducible method (to measure neural density and the neural invasion ratio during conventional histopathological diagnosis of PDAC), which has been validated using another cohort (n = 81).
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Registered trials
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