title: Decreased FOXD3 Expression Is Associated with Poor Prognosis in Patients with High-Grade Gliomas.
abstract: BACKGROUND
  The transcription factor forkhead box D3 (FOXD3) plays important roles in the development of neural crest and has been shown to suppress the development of various cancers. However, the expression and its potential biological roles of FOXD3 in high-grade gliomas (HGGs) remain unknown.
  
  
  METHODS
  The mRNA and protein expression levels of FOXD3 were examined using real-time quantitative PCR and western blotting in 23 HGG and 13 normal brain samples, respectively. Immunohistochemistry was used to validate the expression FOXD3 protein in 184 HGG cases. The association between FOXD3 expression and the prognosis of HGG patients were analyzed using Kaplan-Meier survival curves and Cox proportional hazards regression models. In addition, we further examined the effects of FOXD3 on the proliferation and serum starvation-induced apoptosis of glioma cells.
  
  
  RESULTS
  In comparison to normal brain tissues, FOXD3 expression was significantly decreased in HGG tissues at both mRNA and protein levels. Immunohistochemistry further validated the expression of FOXD3 in HGG tissues. Moreover, low FOXD3 expression was significantly associated with poor prognosis in HGG patients. Depletion of FOXD3 expression promoted glioma cell proliferation and inhibited serum starvation-induced apoptosis, whereas overexpression of FOXD3 inhibited glioma cell proliferation and promoted serum starvation-induced apoptosis.
  
  
  CONCLUSIONS
  Our results indicated that FOXD3 might serve as an independent prognostic biomarker and a potential therapeutic target for HGGs, which warrant further investigation.
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Du
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Changhe
authors.initials: C
authors.lastname: Pang
authors.affiliation: Department of Neurosurgery, Peking University People's Hospital, Beijing, 100044, China.
authors.forename: Dongliang
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Peking University People's Hospital, Beijing, 100044, China.
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Yake
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Jiao
authors.affiliation: Department of Gastroenterology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhan
authors.affiliation: Prenatal Diagnosis Center, Department of Gynecology and Obstetrics, the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Xinting
authors.initials: X
authors.lastname: Wei
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D020868:Gene Silencing / Q000187:drug effects; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D011379:Prognosis; D055815:Young Adult
chemical_list: D016895:Culture Media, Serum-Free; C503514:FOXD3 protein, human; D051858:Forkhead Transcription Factors