title: TPX2 expression is associated with cell proliferation and patient outcome in esophageal squamous cell carcinoma.
abstract: BACKGROUND
  The molecular and genetic changes underlying esophageal squamous cell carcinoma (ESCC) tumor formation and rapid progression are poorly understood. Using high-throughput data analysis, we examined molecular changes involved in ESCC pathogenesis and investigated their clinical relevance.
  
  
  METHODS
  Five independent microarray datasets were examined for differentially expressed genes and pathways. For validation, mRNA expression in tumor and matched normal tissues from 16 ESCC cases was examined by cDNA microarray, and protein expression in 97 ESCC specimens was investigated using immunohistochemical stains. The association between clinicopathological parameters and the expression of Aurora kinase A (Aurora-A) and TPX2 was analyzed. The impact of TPX2 expression was also assessed in ESCC cancer cells.
  
  
  RESULTS
  AURKA and TPX2, members of the "Role of Ran in mitotic spindle regulation" pathway, were selected for further investigation. Verification by cDNA microarray showed that both genes were overexpressed in tumor tissues, and immunohistochemical staining showed Aurora-A and TPX2 expression in 88.4 and 90.6 % of ESCC specimens, respectively. High TPX2 expression was a significant prognosticator for overall and disease-free survival in univariate analysis and remained an independent prognostic factor in multivariate analysis (HR 1.802, p = 0.037). TPX2 knockdown clones showed inhibited cellular proliferation in growth curve studies and formed fewer colonies in the clonogenic assay.
  
  
  CONCLUSIONS
  Using bioinformatics resources, which were validated by microarray analysis and immunohistochemistry stains, and manipulation of TPX2 expression in ESCC cell lines, we demonstrated that TPX2 expression is associated with cell proliferation and poor prognosis among patients with resected ESCC.
authors: Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, hsupokuei@yahoo.com.tw.
authors: Po-Kuei
authors: PK
authors: Hsu
authors: Hsuan-Yu
authors: HY
authors: Chen
authors: Yi-Chen
authors: YC
authors: Yeh
authors: Chueh-Chuan
authors: CC
authors: Yen
authors: Yu-Chung
authors: YC
authors: Wu
authors: Chung-Ping
authors: CP
authors: Hsu
authors: Wen-Hu
authors: WH
authors: Hsu
authors: Teh-Ying
authors: TY
authors: Chou
mesh_terms: D000368:Aged; D064096:Aurora Kinase A / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D018797:Cell Cycle Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D019295:Computational Biology; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057166:High-Throughput Screening Assays; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D009687:Nuclear Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger; D015996:Survival Rate
chemical_list: D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C122167:TPX2 protein, human; C576917:AURKA protein, human; D064096:Aurora Kinase A
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