Liu Qian, Wang Jianpeng, Yang Hongye, Gao Hua, Li Chuzhong, Lan Xiaolei, Zhang Yazhuo
1 Beijing Neurosurgical Institute, Capital Medical University , Beijing, China.
4 Key Laboratory of Central Nervous System Injury Research, Beijing Institute for Brain Disorders Brain Tumor Center, China National Clinical Research Center for Neurological Diseases, Capital Medical University, Beijing, China.
Hum Gene Ther. 2018 Apr 2. doi: 10.1089/hum.2017.200.
Invasiveness of growth hormone-producing pituitary adenomas (GHPAs) causes difficulties in safe and complete adenoma removal during surgery and often leads to high recurrence. Epidermal growth factor-like domain 7 (EGFL7) has been shown to be able to promote tumor angiogenesis, growth, invasiveness, and metastasis through the Notch signaling pathway. It was previously demonstrated that EGFL7 was overexpressed in GHPAs. This study reports that EGFL7 and Notch2 (positive correlation with EGFL7) are overexpressed in invasive GHPA. A long-rank test (Kaplan-Meier method) shows that invasive GHPAs with EGFL7 strong expression results in reduced recurrence-free survival. Multivariate Cox regression analysis reveals that weak EGFL7 expression is an independent prognostic factor for recurrence-free survival. In addition, knockdown of EGFL7 expression suppresses proliferation and invasion of GH3 and GT1-1 cells in vitro. Moreover, attenuation of EGFL7 inhibits human GHPA growth in vivo. The data suggest that as a Notch agonist, EGFL7 may potentially be an appropriate novel molecular target for future development of GHPA medical therapy.
生长激素分泌型垂体腺瘤（GHPA）的侵袭性使得手术中安全、完整地切除腺瘤存在困难，且常常导致高复发率。表皮生长因子样结构域7（EGFL7）已被证明能够通过Notch信号通路促进肿瘤血管生成、生长、侵袭和转移。先前的研究表明，EGFL7在GHPA中过度表达。本研究报告称，EGFL7和Notch2（与EGFL7呈正相关）在侵袭性GHPA中过度表达。长期秩检验（Kaplan-Meier法）显示，EGFL7强表达的侵袭性GHPA导致无复发生存期缩短。多变量Cox回归分析表明，EGFL7低表达是无复发生存期的独立预后因素。此外，敲低EGFL7表达可抑制体外培养的GH3和GT1-1细胞的增殖和侵袭。而且，EGFL7的减弱可抑制体内人GHPA的生长。这些数据表明，作为一种Notch激动剂，EGFL7可能是未来GHPA药物治疗开发的合适新型分子靶点。
