title: Twist1 is an independent prognostic factor of esophageal squamous cell carcinoma and associated with its epithelial-mesenchymal transition.
abstract: BACKGROUND
  Twist1 is known to be involved in epithelial-mesenchymal transition (EMT) and tumor progression. However, its specific role is different depending on the type of cancer. The functional role and clinical significance of Twist1 in esophageal squamous cell carcinoma (ESCC) have been rarely studied.
  
  
  METHODS
  We examined Twist1 expression in a total of 199 samples using immunohistochemistry and real-time reverse-transcription polymerase chain reaction (RT-PCR). We also studied the association of Twist1 with EMT of ESCC using tissue samples and in vitro models. In addition, we examined the changes in the whole-genome expression profiles of two ESCC cell lines after inducing upregulation of Twist1.
  
  
  RESULTS
  Twist1 expression was increased in ESCC compared with that of normal esophagus (P < 0.01). We found that expression of Twist1 was strongly associated with poor prognosis on both univariate analysis [relative risk (RR) = 3.019, P = 0.000] and multivariate analysis (RR = 3.131, P = 0.000). In addition, we found that Twist1 expression was strongly correlated with EMT in ESCC tissues. Upregulation of Twist1 induced other EMT inducers in all three esophageal cancer cell lines investigated (TE1, TE8, and TE10). Twist1 also enhanced the migratory and invasive abilities of all three cell lines. Finally, microarray analysis of gene expression in the three ESCC cell lines revealed that Twist1 upregulation affected the expression of mainly cytoskeleton and extracellular matrix-related genes, which are directly related to cell morphology and movement.
  
  
  CONCLUSIONS
  Our study indicates that Twist1 is associated with EMT of esophageal squamous cell carcinoma and may be used as a diagnostic and prognostic biomarker in ESCC.
authors: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul, Korea.
authors: Keun-Woo
authors: KW
authors: Lee
authors: Jeong Hoon
authors: JH
authors: Kim
authors: Songying
authors: S
authors: Han
authors: Chang-Ohk
authors: CO
authors: Sung
authors: In-Gu
authors: IG
authors: Do
authors: Young-Hyeh
authors: YH
authors: Ko
authors: Sung Hee
authors: SH
authors: Um
authors: Seok-Hyung
authors: SH
authors: Kim
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D016022:Case-Control Studies; D058750:Epithelial-Mesenchymal Transition; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D051879:Twist-Related Protein 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; D012333:RNA, Messenger; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1