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

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-13R?2) 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-13R?2 by IHC and ISH in grade 2 and 3 tumors, while ?64% stage II and III tumors overexpressed IL-13R?2 (?2+). Interestingly, ?36 % peripancreatic neural plexus (PL) and ?70% nerve endings (Ne) among PNI in PDAC samples showed higher levels of IL-13R?2 (?2+). IL-13R?2 +ve PL and Ne subjects survived significantly less than IL-13R?2 -ve subjects, suggesting that IL-13R?2 may have a unique role as a biomarker of PNI-aggressiveness. Importantly, IL-13R?2 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?2 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.

SUBMITTER: Fujisawa T

PROVIDER: S-EPMC7281570 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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

Fujisawa Toshio T Shimamura Takeshi T Goto Kaku K Nakagawa Ryo R Muroyama Ryosuke R Ino Yoshinori Y Horiuchi Hajime H Endo Itaru I Maeda Shin S Harihara Yasushi Y Nakajima Atsushi A Matsuhashi Nobuyuki N Kato Naoya N Isayama Hiroyuki H Puri Ankit A Suzuki Akiko A Bellayr Ian I Leland Pamela P Joshi Bharat H BH Puri Raj K RK

Cancers 20200520 5

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 gra ...[more]

PMID: 32443847

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Project description:BACKGROUND:Cachexia is responsible for the low quality of life in pancreatic adenocarcinoma (PDAC). The rapid disease progression and patient deterioration seems related to perineural invasion, but the relationship between cachexia and perineural invasion for the evolution of the disease has been rarely studied. As perineural invasion is difficult to be highlighted, a biomarker such as the neurotrophic factor Midkine (MK) which promotes the neuronal differentiation and the cell migration could be helpful. Also, Activin (ACV) has been described as cachexia related to PDAC. However, their role for assessing and predicting the disease course in daily practice is not known. AIM:To assess the relationship between perineural invasion and cachexia and their biomarkers, MK and ACV, respectively, and their prognostic value. METHODS:This study included prospectively enrolled patients with proven adenocarcinoma and a matched group of controls without any malignancies. Patients with other causes of malnutrition were excluded. The plasma levels of ACV and MK were analyzed using western blotting and were correlated with the clinicopathological features and survival data. These results were validated by immunohistochemical analyses of the pancreatic tumor tissue of the patients included in the study and a supplementary group of surgically resected specimens from patients with a benign disease. RESULTS:The study comprised 114 patients with PDAC, 125 controls and a supplementary group of 14 benign pancreatic tissue samples. ACV and MK were both overexpressed more frequently in the plasma of patients with PDAC than in the controls (63% vs 32% for ACV, P < 0.001; 47% vs 16% for MK, P < 0.001), with similar levels in pancreatic tissue the MK protein expression was closely related to the advanced clinical stage (P = 0.006), the presence of metastasis (P = 0.04), perineural invasion (P = 0.03) and diabetes (P = 0.002), but with no influence on survival. No correlation between clinicopathological factors and ACV expression was noted. Cachexia, present in 19% of patients, was unrelated to ACV or MK level. Higher ACV expression was associated with a shorter survival (P = 0.008). CONCLUSION:The MK was a biomarker of perineural invasion, associated with tumor stage and diabetes, but without prognostic value as ACV. Cachexia was unrelated to perineural invasion, ACV level or survival.

Dataset Information

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

Publications

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

Similar Datasets

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