title: Upregulation of Twist in oesophageal squamous cell carcinoma is associated with neoplastic transformation and distant metastasis.
abstract: BACKGROUND
  The antiapoptotic and epithelial-mesenchymal transition activities of Twist have been implicated in the neoplastic transformation and the development of metastasis, respectively. Upregulation of Twist, described in several types of human cancer, also acts as a prognostic marker of poor outcome.
  
  
  OBJECTIVE
  To investigate Twist expression in oesophageal squamous cell carcinoma (SCC) and its prognostic value in a Chinese cohort of patients with oesophageal SCC.
  
  
  METHODS
  Twist expression in primary oesophageal SCC of 87 Chinese patients was investigated by immunohistochemical staining. Twist protein level in one immortalised normal oesophageal epithelial cell line and six oesophageal SCC cell lines was measured by western blot analysis. Twist mRNA level in 30 pairs of frozen specimens of primary oesophageal SCC and non-neoplastic oesophageal epithelium from the upper resection margin of corresponding oesophagectomy specimen was also determined by semiquantitative reverse transcription-PCR.
  
  
  RESULTS
  It was found that Twist was upregulated in oesophageal SCC cell lines, and its mRNA and protein levels were both increased in oesophageal SCC and the non-neoplastic oesophageal epithelium (p<0.001). In addition, a high level of Twist expression in oesophageal SCC was significantly associated with a greater risk for the patient of developing distant metastasis within 1 year of oesophagectomy (OR 3.462, 95% CI 1.201 to 9.978; p=0.022).
  
  
  CONCLUSIONS
  Our results suggest that upregulation of Twist plays a role in the neoplastic transformation to oesophageal SCC and subsequent development of distant metastasis. Twist may serve as a useful prognostic marker for predicting the development of distant metastasis in oesophageal SCC.
authors.affiliation: Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Hiu-Fung
authors.initials: HF
authors.lastname: Yuen
authors.forename: Yuen-Piu
authors.initials: YP
authors.lastname: Chan
authors.forename: Michelle Lok-Yee
authors.initials: ML
authors.lastname: Wong
authors.forename: Wei-Kei
authors.initials: WK
authors.lastname: Kwok
authors.forename: Ka-Kui
authors.initials: KK
authors.lastname: Chan
authors.forename: Pin-Yin
authors.initials: PY
authors.lastname: Lee
authors.forename: Gopesh
authors.initials: G
authors.lastname: Srivastava
authors.forename: Simon Ying-Kit
authors.initials: SY
authors.lastname: Law
authors.forename: Yong-Chuan
authors.initials: YC
authors.lastname: Wong
authors.forename: Xianghong
authors.initials: X
authors.lastname: Wang
authors.forename: Kwok-Wah
authors.initials: KW
authors.lastname: Chan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000556:secondary / Q000601:surgery; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D016629:Esophagectomy; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014407:Tumor Cells, Cultured; D051879:Twist-Related Protein 1 / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1