机构：[1]Beijing Neurosurgical Institute, Capital Medical University, Beijing, China研究所北京市神经外科研究所首都医科大学附属天坛医院[2]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China重点科室诊疗科室神经外科神经外科首都医科大学附属天坛医院[3]Beijing Institute for Brain Disorders, Brain Tumor Center, Beijing, China National Clinical Research Center for Neurological Diseases, Beijing, China
Background The detection and treatment of invasive growth hormone-secreting pituitary adenoma (GHPA) remains challenging. Several transcription factors promoting the epithelial-mesenchymal transition (EMT) can act as cofactors for the transforming growth factor-beta (TGF-ss)/SMAD4. The goal of this study was to investigate the association of SMAD4 expression and clinicopathologic features using a tissue microarray analysis (TMA). The levels of SMAD4 and the related genes of EMT in GHPAs were analyzed by q-PCR and western blot. SMAD4 was strongly expressed in 15/19 cases (78.9%) of invasive GHPA and 10/42 cases (23.8%) of noninvasive GHPA (X-2=10.887, p=0.000). In the high SMAD4 group, a headache was reported in 16/25 cases (64%) compared with 13/36 cases (36.1%) in the low SMAD4 group (X-2=4.565, p=0.032). The progression-free survival (PFS) in the high group was lower than that in the low group (p=0.026). qRT-PCR and western blot analysis further revealed a significant downregulation of E-cadherin and upregulation of N-cadherin and vimentin in the invasive GHPA group. SMAD4 was associated with increased levels of invasion of GH3 cells, as determined by a transwell test. SMAD4 downregulated E-cadherin levels and increased the levels of N-cadherin and vimentin. Our data provide evidence that SMAD4 is a potential prognosis biomarker and a therapeutic target for patients with invasive GHPA.
基金：
National High-tech Research and Development Program of China (863 Program) [2015AA020504]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81601205]; Beijing Natural Science Foundation of ChinaBeijing Natural Science Foundation [7162035]; Beijing High-level Talent Plan [2015-3-040]
第一作者机构：[1]Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
通讯作者：
通讯机构：[*1]Beijing Neurosurgical Institute, Capital Medical University, Beijing, China[*2]Beijing Institute for Brain Disorders, Brain Tumor Center, Beijing, China National Clinical Research Center for Neurological Diseases, Beijing, China
推荐引用方式(GB/T 7714)：
Xiaosong Shan,Qian Liu,Chuzhong Li,et al.Epithelial-Mesenchymal Transition Induced by SMAD4 Activation in Invasive Growth Hormone-Secreting Adenomas[J].OPEN CHEMISTRY.2018,16(1):571-582.doi:10.1515/chem-2018-0061.
APA：
Xiaosong Shan,Qian Liu,Chuzhong Li,Hua Gao,Zhenye Li...&Yazhuo Zhang.(2018).Epithelial-Mesenchymal Transition Induced by SMAD4 Activation in Invasive Growth Hormone-Secreting Adenomas.OPEN CHEMISTRY,16,(1)
MLA：
Xiaosong Shan,et al."Epithelial-Mesenchymal Transition Induced by SMAD4 Activation in Invasive Growth Hormone-Secreting Adenomas".OPEN CHEMISTRY 16..1(2018):571-582
