title: Twist1 correlates with poor differentiation and progression in gastric adenocarcinoma via elevation of FGFR2 expression.
abstract: OBJECTIVE
  To explore the correlation between Twist-related protein (Twist)1, fibroblast growth factor receptor (FGFR)2 and gastric adenocarcinoma differentiation and progression.
  
  
  METHODS
  We evaluated Twist1 and FGFR2 in 52 gastric adenocarcinoma samples by immunohistochemistry and quantitative real time polymerase chain reaction, and analyzed the correlation between Twist1, FGFR2 and cancer differentiation. We also detected Twist1 and FGFR2 expression in gastric adenocarcinoma cell lines, and evaluated Twist1 influence on FGFR2 expression. In addition, we studied the role of FGFR2 in Twist1-promoted cancer progression, including proliferation, invasion and epithelial-mesenchymal transition (EMT).
  
  
  RESULTS
  Twist1 and FGFR2 were detected in almost all the gastric adenocarcinoma samples. Twist1 (P = 0.0213) and FGFR2 (P = 0.0310) mRNA levels had a significant association with gastric adenocarcinoma differentiation. Moreover, Twist1 and FGFR2 expression in poorly differentiated cells (SNU-1 and SNU-16) was notably higher than in well-differentiated cells (MKN-7 and MKN-28). In poorly differentiated gastric adenocarcinomas, FGFR2 mRNA level was significantly positively correlated with Twist1 mRNA level (P = 0.004). Twist1 was proved to promote FGFR2 by regulating Twist1 expression by knockdown and overexpression. Additionally, Twist1 could induce proliferation, invasion and EMT in gastric cancer; of these, FGFR2 was required for invasion and EMT, rather than proliferation.
  
  
  CONCLUSIONS
  Twist1 and FGFR2 are highly associated with differentiation of gastric adenocarcinoma; Twist1 can facilitate invasion and EMT in gastric adenocarcinoma via promotion of FGFR2 expression.
authors.affiliation: Dong-Yuan Zhu, Qi-Sen Guo, Yan-Liang Li, Department of Medical Oncology, Shandong Cancer Hospital and Institute, Jinan 250117, Shandong Province, China.
authors.forename: Dong-Yuan
authors.initials: DY
authors.lastname: Zhu
authors.affiliation: Dong-Yuan Zhu, Qi-Sen Guo, Yan-Liang Li, Department of Medical Oncology, Shandong Cancer Hospital and Institute, Jinan 250117, Shandong Province, China.
authors.forename: Qi-Sen
authors.initials: QS
authors.lastname: Guo
authors.affiliation: Dong-Yuan Zhu, Qi-Sen Guo, Yan-Liang Li, Department of Medical Oncology, Shandong Cancer Hospital and Institute, Jinan 250117, Shandong Province, China.
authors.forename: Yan-Liang
authors.initials: YL
authors.lastname: Li
authors.affiliation: Dong-Yuan Zhu, Qi-Sen Guo, Yan-Liang Li, Department of Medical Oncology, Shandong Cancer Hospital and Institute, Jinan 250117, Shandong Province, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Cui
authors.affiliation: Dong-Yuan Zhu, Qi-Sen Guo, Yan-Liang Li, Department of Medical Oncology, Shandong Cancer Hospital and Institute, Jinan 250117, Shandong Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.affiliation: Dong-Yuan Zhu, Qi-Sen Guo, Yan-Liang Li, Department of Medical Oncology, Shandong Cancer Hospital and Institute, Jinan 250117, Shandong Province, China.
authors.forename: Ji-Xiao
authors.initials: JX
authors.lastname: Liu
authors.affiliation: Dong-Yuan Zhu, Qi-Sen Guo, Yan-Liang Li, Department of Medical Oncology, Shandong Cancer Hospital and Institute, Jinan 250117, Shandong Province, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014162:Transfection; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; D012333:RNA, Messenger; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2
keywords: Cancer differentiation; Cancer progression; Fibroblast growth factor receptor 2; Gastric adenocarcinoma; Twist-related protein 1