Attenuation of EGFL7 Expression Inhibits Growth Hormone-Producing Pituitary Adenomas Growth and Invasion.

in Human gene therapy by Qian Liu, Jianpeng Wang, Hongye Yang, Hua Gao, Chuzhong Li, Xiaolei Lan, Yazhuo Zhang

TLDR

  • The study found that EGFL7 and Notch2 are overexpressed in invasive GHPAs, leading to reduced recurrence-free survival, and identifies EGFL7 as a potential novel molecular target for future medical therapy.

Abstract

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.

Overview

  • The study aimed to investigate the relationship between EGFL7 and Notch2 in invasive growth hormone-producing pituitary adenomas (GHPAs) and their effects on recurrence-free survival.
  • The study used a combination of in vitro and in vivo experiments to explore the role of EGFL7 in GHPAs, including its correlation with Notch2, cell proliferation, invasion, and tumor growth.
  • The primary objective of the study was to identify potential therapeutic targets for GHPAs, specifically EGFL7, as a novel molecular target for future medical therapy.

Comparative Analysis & Findings

  • The study found that EGFL7 and Notch2 are overexpressed in invasive GHPAs, with a positive correlation between the two.
  • A long-rank test showed that invasive GHPAs with strong EGFL7 expression exhibited reduced recurrence-free survival, while weak EGFL7 expression was an independent prognostic factor for recurrence-free survival.
  • In vitro and in vivo experiments revealed that knockdown of EGFL7 expression suppressed proliferation and invasion of GH3 and GT1-1 cells, as well as human GHPA growth.

Implications and Future Directions

  • The study suggests that EGFL7 may be a potential novel molecular target for the treatment of GHPAs, particularly as a Notch agonist.
  • Further research is needed to fully understand the mechanisms by which EGFL7 contributes to GHPA invasiveness and recurrence, as well as to develop EGFL7-targeted therapies.
  • The identification of EGFL7 as a prognostic factor and potential therapeutic target for GHPAs may lead to improved treatment options for patients with these aggressive tumors.
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