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SPARC is associated with tumor nerve stroma interactions and perineural invasion in pancreatic ductal adenocarcinoma.

Overview

Authors: Satoru Furuhashi1,2, Ryuta Muraki1,2,3, Yoshifumi Morita1, Daiki Nishiwaki1, Akio Matsumoto1, Yuji Shimizu1, Tomohiro Murakami1, Makoto Takeda1, Hirotoshi Kikuchi1, Yoshihiro Hiramatsu1,4, Tomoaki Kahyo2, Mitsutoshi Setou2,5,6, Hiroya Takeuchi1
  1. Department of Surgery, Hamamatsu University School of Medicine, 1-20-1, Handayama, Chuou-ku, Hamamatsu, 431-3125 Shizuoka Japan
  2. Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Japan
  3. Department of Gastroenterological Surgery, Shizuoka General Hospital, Shizuoka, Shizuoka Japan
  4. Department of Perioperative Functioning Care and Support, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka Japan
  5. International Mass Imaging Center, Hamamatsu University School of Medicine, Hamamatsu, Japan
  6. Department of Systems Molecular Anatomy, Institute for Medical Photonics Research, Preeminent Medical Photonics Education & Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan
Institutions: Hamamatsu University (Japan); Hamamatsu University School of Medicine (Japan); Shizuoka General Hospital (Japan)
Journal: Scientific reports, volume 16, issue 1, article 24293
Dates: received 16 October 2025; accepted 30 April 2026; published online 11 May 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41598-026-51848-6 · PMID 42115728 · PMCID PMC13442835 · OpenAlex W7160849158
Open access: gold, a free copy (OpenAlex)
Status: code on request
Categories: genetics / omics (modality), human (organism), mouse (organism), other condition (population)
Methods: Statistics, Smoothing, state filtering, decompositions, Machine learning, Preprocessing, Connectivity, fMRI & imaging
Keywords: Pancreatic ductal adenocarcinoma, Perineural invasion, Tumor microenvironment, Proteomics, SPARC, Biomarkers, Cancer, Oncology
MeSH: Carcinoma, Pancreatic Ductal*, Osteonectin*, Pancreatic Neoplasms*, Animals, Cell Line, Tumor, Cell Movement, Coculture Techniques, Female, Ganglia, Spinal, Gene Expression Regulation, Neoplastic, Humans, Mice, Neoplasm Invasiveness, Pancreatic Stellate Cells, Peripheral Nerves, Proteomics, Tumor Microenvironment (* major topic)
Topic: Bone and Dental Protein Studies (Rheumatology, Medicine), according to OpenAlex
Funding: Japan Society for the Promotion of Science (20K22838)
Citations: not cited yet (Europe PMC); 33 references in the paper

Abstract

Perineural invasion (PNI) is frequent in pancreatic ductal adenocarcinoma (PDAC) and contributes to poor prognosis, yet stromal–neural mechanisms remain unclear. We developed a vertical multi-co-culture model incorporating human PDAC cells, neonatal mouse dorsal root ganglion (DRG) neurons, and human pancreatic stellate cells (PSCs). Migration assays demonstrated markedly greater PDAC cell migration in DRG + PSC than either condition alone. Proteomic profiling of conditioned media identified Secreted Protein Acidic and Rich in Cysteine (SPARC) as a highly enriched factor in the DRG + PSC condition. Public transcriptomic datasets (TCGA, GTEx, scRNA-seq) confirmed SPARC upregulation in PDAC, with predominant expression in fibroblasts and association with poor survival. Immunohistochemistry of 81 resected PDAC specimens in Hamamatsu University School of Medicine revealed stromal-rich SPARC expression significantly correlated with PNI-positive status. Collectively, these findings indicate that stromal SPARC is associated with PNI-related aggressiveness in PDAC. SPARC may serve as a biomarker of unfavorable prognosis and as a candidate stromal factor warranting future functional validation within the tumor-nerve-stromal axis.

Supplementary Information: The online version contains supplementary material available at 10.1038/s41598-026-51848-6.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

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Data

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Data availability

All data supporting the findings of this study are included in the article and its Supplementary Information. De-identified raw data and analysis code are available from the corresponding author upon reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 13 authors, 8 keywords, 17 MeSH terms, 1 funder, 33 references.

Cite

This paper

Furuhashi, S., Muraki, R., Morita, Y., Nishiwaki, D., Matsumoto, A., Shimizu, Y., Murakami, T., Takeda, M., Kikuchi, H., Hiramatsu, Y., Kahyo, T., Setou, M., & Takeuchi, H. (2026). SPARC is associated with tumor nerve stroma interactions and perineural invasion in pancreatic ductal adenocarcinoma. Scientific reports, 16(1), 24293. https://doi.org/10.1038/s41598-026-51848-6

BibTeX

@article{furuhashi2026sparc,
author = {Furuhashi, Satoru and Muraki, Ryuta and Morita, Yoshifumi and Nishiwaki, Daiki and Matsumoto, Akio and Shimizu, Yuji and Murakami, Tomohiro and Takeda, Makoto and Kikuchi, Hirotoshi and Hiramatsu, Yoshihiro and Kahyo, Tomoaki and Setou, Mitsutoshi and Takeuchi, Hiroya},
title = {{SPARC is associated with tumor nerve stroma interactions and perineural invasion in pancreatic ductal adenocarcinoma}},
journal = {Scientific reports},
year = {2026},
month = may,
volume = {16},
number = {1},
pages = {24293},
publisher = {Nature Publishing Group},
issn = {2045-2322},
doi = {10.1038/s41598-026-51848-6},
url = {https://doi.org/10.1038/s41598-026-51848-6},
pmid = {42115728},
pmcid = {PMC13442835}
}

RIS

TY - JOUR
AU - Furuhashi, Satoru
AU - Muraki, Ryuta
AU - Morita, Yoshifumi
AU - Nishiwaki, Daiki
AU - Matsumoto, Akio
AU - Shimizu, Yuji
AU - Murakami, Tomohiro
AU - Takeda, Makoto
AU - Kikuchi, Hirotoshi
AU - Hiramatsu, Yoshihiro
AU - Kahyo, Tomoaki
AU - Setou, Mitsutoshi
AU - Takeuchi, Hiroya
TI - SPARC is associated with tumor nerve stroma interactions and perineural invasion in pancreatic ductal adenocarcinoma
T2 - Scientific reports
J2 - Sci Rep
PY - 2026
DA - 2026/05/11
VL - 16
IS - 1
SP - 24293
SN - 2045-2322
PB - Nature Publishing Group
DO - 10.1038/s41598-026-51848-6
UR - https://doi.org/10.1038/s41598-026-51848-6
LA - en
ER -

CSL-JSON

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