KIAA1199/CEMIP/HYBID高表达预示胰腺导管腺癌预后不良。

KIAA1199/CEMIP/HYBID overexpression predicts poor prognosis in pancreatic ductal adenocarcinoma.

作者信息

Koga Atsuhiro, Sato Norihiro, Kohi Shiro, Yabuki Kei, Cheng Xiao-Bo, Hisaoka Masanori, Hirata Keiji

机构信息

Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.

出版信息

Pancreatology. 2017 Jan-Feb;17(1):115-122. doi: 10.1016/j.pan.2016.12.007. Epub 2016 Dec 18.

DOI:10.1016/j.pan.2016.12.007

PMID:28012880

Abstract

BACKGROUND

KIAA1199 (also known as CEMIP or HYBID), a newly identified protein involved in hyaluronan degradation, has been suggested to play a critical role in cancer progression. The aim of this study was to investigate the expression and functional significance of KIAA1199 in pancreatic ductal adenocarcinoma (PDAC).

METHODS

Using quantitative real-time RT-PCR, we analyzed KIAA1199 mRNA expression in 6 PDAC cell lines and frozen tissues from 14 patients with PDAC. We also used immunohistochemistry to analyze KIAA1199 protein expression in formalin-fixed, paraffin-embedded tissues from 98 patients with PDAC. The KIAA1199 expression pattern was then correlated with clinicopathological variables and patient outcome. The effect of KIAA1199 on migratory ability of PDAC cells was determined by KIAA1199 knockdown with small-interfering RNA (siRNA).

RESULTS

The KIAA1199 mRNA expression was significantly higher in PDAC tissues than in the corresponding non-tumor tissues (P < 0.0001). Immunohistochemical analysis revealed high expression of KIAA1199 in 26 (26.5%) of 98 PDAC tissues. The overall survival was significantly shorter in patients with high KIAA1199 expression than in patients with low KIAA1199 expression (P = 0.0001). In multivariate analysis, high KIAA1199 expression (P = 0.003) and UICC stage (P = 0.003) were independent factors predicting poor prognosis. Furthermore, the KIAA1199 mRNA expression was higher in most PDAC cell lines and siRNA knockdown of KIAA1199 resulted in decreased migration.

CONCLUSION

These findings suggest that overexpression of KIAA1199 may contribute to increased migration of PDAC cells and predict shorter survival after surgical resection.

摘要

背景

KIAA1199（也称为CEMIP或HYBID）是一种新发现的参与透明质酸降解的蛋白质，已被认为在癌症进展中起关键作用。本研究的目的是探讨KIAA1199在胰腺导管腺癌（PDAC）中的表达及功能意义。

方法

使用定量实时逆转录聚合酶链反应（RT-PCR），我们分析了6种PDAC细胞系以及14例PDAC患者冷冻组织中KIAA1199 mRNA的表达。我们还使用免疫组织化学方法分析了98例PDAC患者福尔马林固定、石蜡包埋组织中KIAA1199蛋白的表达。然后将KIAA1199的表达模式与临床病理变量及患者预后相关联。通过小干扰RNA（siRNA）敲低KIAA1199来确定其对PDAC细胞迁移能力的影响。

结果

PDAC组织中KIAA1199 mRNA的表达显著高于相应的非肿瘤组织（P < 0.0001）。免疫组织化学分析显示，98例PDAC组织中有26例（26.5%）KIAA1199高表达。KIAA1199高表达患者的总生存期显著短于低表达患者（P = 0.0001）。多因素分析显示，KIAA1199高表达（P = 0.003）和国际抗癌联盟（UICC）分期（P = 0.003）是预测预后不良的独立因素。此外，大多数PDAC细胞系中KIAA1199 mRNA表达较高，且siRNA敲低KIAA1199导致细胞迁移减少。