title: Both STAT1 and STAT3 are favourable prognostic determinants in colorectal carcinoma.
abstract: BACKGROUND
  Aberrant activities of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signalling pathways have been implicated in the development and spread of various cancer entities, among them colorectal carcinoma (CRC). Transcription factors STAT3 and STAT1, both downstream effectors of interleukin (IL)-6 and its receptor, are involved in growth and developmental control of CRC cells. Constituents of the signalling network around IL-6 and STAT activation are discussed as potential biomarkers and therapeutic targets in CRC.
  
  
  METHODS
  By immunohistochemical analysis of a tissue microarray covering >400 CRC biopsies, the expression and activity status of STAT1, STAT3 as well as of IL-6 and the IL-6 receptor α-chain was determined. The outcome was correlated with clinical information and patients' survival data. Colorectal carcinoma biopsies were also analysed for specific DNA-binding activity of STATs.
  
  
  RESULTS
  Statistical analysis showed tendential associations between individual STATs, IL-6/IL-6 receptor-α and clinicopathological parameters. The study revealed a significant correlation of high STAT1 activity with longer patient overall survival. Surprisingly, strong STAT3 expression in surgical specimens was correlated with an increase in median overall survival by about 30 months. Statistical analysis revealed that high expression levels of STAT1 and STAT3 were associated. This finding was backed up by biochemical data that showed simultaneous STAT1 and STAT3 DNA-binding activity in randomly selected CRC biopsies.
  
  
  CONCLUSIONS
  By multivariate data analysis, we could show that STAT3 expression and activity constitutes an independent favourable prognostic marker for CRC.
authors.affiliation: Institute of Biochemistry II, University Hospital Jena, Jena, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Gordziel
authors.forename: J
authors.initials: J
authors.lastname: Bratsch
authors.forename: R
authors.initials: R
authors.lastname: Moriggl
authors.forename: T
authors.initials: T
authors.lastname: Knösel
authors.forename: K
authors.initials: K
authors.lastname: Friedrich
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D015999:Multivariate Analysis; D011379:Prognosis; D019947:Receptors, Interleukin-6 / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human