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Article

A Novel Role of Interleukin 13 Receptor alpha2 in Perineural Invasion and its Association with Poor Prognosis of Patients with Pancreatic Ductal Adenocarcinoma †

by
Toshio Fujisawa
1,2,3,
Takeshi Shimamura
4,
Kaku Goto
2,
Ryo Nakagawa
2,
Ryosuke Muroyama
2,
Yoshinori Ino
5,
Hajime Horiuchi
6,
Itaru Endo
7,
Shin Maeda
8,
Yasushi Harihara
9,
Atsushi Nakajima
4,
Nobuyuki Matsuhashi
10,
Naoya Kato
2,
Hiroyuki Isayama
1,
Ankit Puri
3,
Akiko Suzuki
3,
Ian Bellayr
3,
Pamela Leland
3,
Bharat H. Joshi
3,* and
Raj K. Puri
3,*
1
Department of Gastroenterology, Juntendo University, Tokyo 113-8421, Japan
2
Division of Advanced Genome Medicine, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
3
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
4
Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
5
Pathology Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan
6
Department of Pathology, NTT Medical Center, Tokyo 141-0022, Japan
7
Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
8
Department of Gastroenterology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
9
Department of Surgery, NTT Medical Center, Tokyo 141-0022, Japan
10
Department of Gastroenterology, NTT Medical Center, Tokyo 141-0022, Japan
*
Authors to whom correspondence should be addressed.
†
Short Title: Role of IL-13Rα2 expression in Perineural Invasion.
Cancers 2020, 12(5), 1294; https://doi.org/10.3390/cancers12051294
Submission received: 13 April 2020 / Revised: 11 May 2020 / Accepted: 16 May 2020 / Published: 20 May 2020
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Abstract

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-13Rα2) 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 ≥75% samples overexpressed IL-13Rα2 by IHC and ISH in grade 2 and 3 tumors, while ≥64% stage II and III tumors overexpressed IL-13Rα2 (≥2+). Interestingly, ≥36 % peripancreatic neural plexus (PL) and ≥70% nerve endings (Ne) among PNI in PDAC samples showed higher levels of IL-13Rα2 (≥2+). IL-13Rα2 +ve PL and Ne subjects survived significantly less than IL-13Rα2 –ve subjects, suggesting that IL-13Rα2 may have a unique role as a biomarker of PNI-aggressiveness. Importantly, IL-13Rα2 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-13Rα2 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.
Keywords: IL-13Rα2; pancreatic ductal adenocarcinoma; prognosis; perineural invasion IL-13Rα2; pancreatic ductal adenocarcinoma; prognosis; perineural invasion

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MDPI and ACS Style

Fujisawa, T.; Shimamura, T.; Goto, K.; Nakagawa, R.; Muroyama, R.; Ino, Y.; Horiuchi, H.; Endo, I.; Maeda, S.; Harihara, Y.; et al. A Novel Role of Interleukin 13 Receptor alpha2 in Perineural Invasion and its Association with Poor Prognosis of Patients with Pancreatic Ductal Adenocarcinoma. Cancers 2020, 12, 1294. https://doi.org/10.3390/cancers12051294

AMA Style

Fujisawa T, Shimamura T, Goto K, Nakagawa R, Muroyama R, Ino Y, Horiuchi H, Endo I, Maeda S, Harihara Y, et al. A Novel Role of Interleukin 13 Receptor alpha2 in Perineural Invasion and its Association with Poor Prognosis of Patients with Pancreatic Ductal Adenocarcinoma. Cancers. 2020; 12(5):1294. https://doi.org/10.3390/cancers12051294

Chicago/Turabian Style

Fujisawa, Toshio, Takeshi Shimamura, Kaku Goto, Ryo Nakagawa, Ryosuke Muroyama, Yoshinori Ino, Hajime Horiuchi, Itaru Endo, Shin Maeda, Yasushi Harihara, and et al. 2020. "A Novel Role of Interleukin 13 Receptor alpha2 in Perineural Invasion and its Association with Poor Prognosis of Patients with Pancreatic Ductal Adenocarcinoma" Cancers 12, no. 5: 1294. https://doi.org/10.3390/cancers12051294

APA Style

Fujisawa, T., Shimamura, T., Goto, K., Nakagawa, R., Muroyama, R., Ino, Y., Horiuchi, H., Endo, I., Maeda, S., Harihara, Y., Nakajima, A., Matsuhashi, N., Kato, N., Isayama, H., Puri, A., Suzuki, A., Bellayr, I., Leland, P., Joshi, B. H., & Puri, R. K. (2020). A Novel Role of Interleukin 13 Receptor alpha2 in Perineural Invasion and its Association with Poor Prognosis of Patients with Pancreatic Ductal Adenocarcinoma. Cancers, 12(5), 1294. https://doi.org/10.3390/cancers12051294

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