Clinical role of Notch signaling pathway in intraductal papillary mucinous neoplasm of the pancreas

被引：18

作者：

Ikemoto, Tetsuya ^{[1
]}

Sugimoto, Koji ^{[1
]}

Shimada, Mitsuo ^{[1
]}

Utsunomiya, Tohru ^{[1
]}

Morine, Yuji ^{[1
]}

Imura, Satoru ^{[1
]}

Arakawa, Yusuke ^{[1
]}

Kanamoto, Mami ^{[1
]}

Iwahashi, Shu-ichi ^{[1
]}

Saito, Yu ^{[1
]}

Yamada, Shinichiro ^{[1
]}

机构：

[1] Univ Tokushima, Inst Hlth Biosci, Dept Surg, Tokushima 7708503, Japan

来源：

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY | 2015年 / 30卷 / 01期

基金：

日本学术振兴会;

关键词：

intraductal papillary mucinous neoplasms; Jagged1; Notch signaling; regulatory T cell; TUMOR-INDUCED TOLERANCE; NF-KAPPA-B; T-CELLS; INDOLEAMINE 2,3-DIOXYGENASE; CANCER PROGRESSION; PERIPHERAL-BLOOD; CARCINOMA; RESECTION; IMMUNITY; GROWTH;

D O I：

10.1111/jgh.12660

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

摘要：

Background and AimThis study was performed to elucidate the expression of the Notch signaling pathway and its correlations to clinicopathological factors of intraductal papillary mucinous neoplasms (IPMNs). It is incontrovertible that regulatory T cells (Tregs) play an important role in tumor immunity. However, the whole mechanism of control of peripheral Tregs remains unclear. It is also known that the Notch signaling pathway is involved in Treg suppressor function. Moreover, IPMNs have a high malignant potential. MethodsPeripheral blood samples and resected specimens from 18 patients with IPMN were evaluated. All patients were pathologically diagnosed with IPMN. Resected specimens were immunohistochemically evaluated (anti-Notch1, anti-Notch2, and anti-Notch2-intracellular domain antibody staining) and compared in terms of clinicopathological factors. Peripheral Treg populations were analyzed with an automated flow cytometer. ResultsDisease-free survival was significantly worse in the Notch1 high-expression group (P=0.023). Notch2 family expressions were higher in intraductal papillary mucinous carcinoma (IPMC) than in intraductal papillary mucinous adenoma (IPMA) (Notch2, P=0.012; Notch2-intracellular domain, P=0.036). Jagged1 expression was significantly higher in IPMC than in IPMA (P<0.05) and was significantly related to recurrence. The Treg population in peripheral blood was higher in patients with IPMC than in those with IPMA (P<0.01). ConclusionsNotch signaling, especially Jagged1 expression, reflects IPMN aggressiveness. Our data may suggest that the Notch signaling pathway is a key pathway that determines IPMN pathological aggressiveness and reflects the peripheral Treg population.

引用

页码：217 / 222

页数：6

共 30 条

[1]

Notch1 signaling and regulatory T cell function [J].