{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T21:49:38Z","timestamp":1772574578676,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T00:00:00Z","timestamp":1589932800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["JP18K07332"],"award-info":[{"award-number":["JP18K07332"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Perineural invasion (PNI) is one of the major pathological characteristics of pancreatic ductal adeno-carcinoma (PDAC), which is mediated by invading cancer cells into nerve cells. Herein, we identify the overexpression of Interleukin-13 Receptor alpha2 (IL-13R\u03b12) in the PNI from 236 PDAC samples by studying its expression at the protein levels by immunohistochemistry (IHC) and the RNA level by in situ hybridization (ISH). We observe that \u226575% samples overexpressed IL-13R\u03b12 by IHC and ISH in grade 2 and 3 tumors, while \u226564% stage II and III tumors overexpressed IL-13R\u03b12 (\u22652+). Interestingly, \u226536 % peripancreatic neural plexus (PL) and \u226570% nerve endings (Ne) among PNI in PDAC samples showed higher levels of IL-13R\u03b12 (\u22652+). IL-13R\u03b12 +ve PL and Ne subjects survived significantly less than IL-13R\u03b12 \u2013ve subjects, suggesting that IL-13R\u03b12 may have a unique role as a biomarker of PNI-aggressiveness. Importantly, IL-13R\u03b12 may be a therapeutic target for intervention, which might not only prolong patient survival but also help alleviate pain attributed to perineural invasion. Our study uncovers a novel role of IL-13R\u03b12 in PNI as a key factor of the disease severity, thus revealing a therapeutically targetable option for PDAC and to facilitate PNI-associated pain management.<\/jats:p>","DOI":"10.3390\/cancers12051294","type":"journal-article","created":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T10:37:38Z","timestamp":1589971058000},"page":"1294","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["A Novel Role of Interleukin 13 Receptor alpha2 in Perineural Invasion and its Association with Poor Prognosis of Patients with Pancreatic Ductal Adenocarcinoma"],"prefix":"10.3390","volume":"12","author":[{"given":"Toshio","family":"Fujisawa","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Juntendo University, Tokyo 113-8421, Japan"},{"name":"Division of Advanced Genome Medicine, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan"},{"name":"Tumor Vaccines and Biotechnology Branch, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Shimamura","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaku","family":"Goto","sequence":"additional","affiliation":[{"name":"Division of Advanced Genome Medicine, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryo","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Division of Advanced Genome Medicine, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryosuke","family":"Muroyama","sequence":"additional","affiliation":[{"name":"Division of Advanced Genome Medicine, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshinori","family":"Ino","sequence":"additional","affiliation":[{"name":"Pathology Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hajime","family":"Horiuchi","sequence":"additional","affiliation":[{"name":"Department of Pathology, NTT Medical Center, Tokyo 141-0022, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Itaru","family":"Endo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama 236-0004, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shin","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasushi","family":"Harihara","sequence":"additional","affiliation":[{"name":"Department of Surgery, NTT Medical Center, Tokyo 141-0022, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6263-1436","authenticated-orcid":false,"given":"Atsushi","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0139-430X","authenticated-orcid":false,"given":"Nobuyuki","family":"Matsuhashi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, NTT Medical Center, Tokyo 141-0022, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoya","family":"Kato","sequence":"additional","affiliation":[{"name":"Division of Advanced Genome Medicine, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Isayama","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Juntendo University, Tokyo 113-8421, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ankit","family":"Puri","sequence":"additional","affiliation":[{"name":"Tumor Vaccines and Biotechnology Branch, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akiko","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Tumor Vaccines and Biotechnology Branch, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian","family":"Bellayr","sequence":"additional","affiliation":[{"name":"Tumor Vaccines and Biotechnology Branch, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamela","family":"Leland","sequence":"additional","affiliation":[{"name":"Tumor Vaccines and Biotechnology Branch, Division of Cellular and Gene 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