title: The clinical and biological significance of STAT1 in esophageal squamous cell carcinoma.
abstract: BACKGROUND
  Loss of STAT1 (Signal Transducer and Activator of Transcription-1) has been implicated in the pathobiology of a number of cancer types. Nonetheless, the biological and clinical significance of STAT1 in esophageal squamous cell carcinomas (ESCC) has not been comprehensively studied.
  
  
  METHODS
  Using immunohistochemistry, we detected the STAT1 expression in a cohort of ESCC patients; In-vitro experiments, we used enforced gene transfection of STAT1C into two STAT1- weak/negative ESCC cell lines and siRNA knockdown of STAT1 in two STAT1-strong ESCC cell lines to detect STAT1 function in ESCC.
  
  
  RESULTS
  We found that the expression of STAT1 was heterogeneous in ESCC, with 64 (49.0%) strongly positive cases, 59 (45.0%) weakly positive cases and 8 (6.1%) negative cases. STAT1 expression inversely correlated with the depth of tumor invasion and tumor size (p=0.047 and p=0.029, respectively, Chi square). Furthermore, patients with STAT1-strong/weak tumors had a significantly longer survival compared to those with STAT1-negative tumors (33.6 months versus 13.1 months, p=0.019). In patients carrying tumors of aggressive cytology (n=50), those with STAT1-strong tumors survived significantly longer than those with STAT1-weak/negative tumors (34.6 months versus 20.5 months, p=0.011). Our in-vitro experiments revealed that STAT1 is proapoptotic and inhibitory to cell-cycle progression and colony formation. Lastly, we found evidence that STAT1 signaling in ESCC cells down-regulated the expression and/or activity of NF-κB and STAT3, both of which are known to have oncogenic potential.
  
  
  CONCLUSIONS
  To conclude, our findings suggest that STAT1 is a tumor suppressor in ESCC. Loss of STAT1, which is frequent in ESCC, contributes to the pathogenesis of these tumors.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ommoleila
authors.initials: O
authors.lastname: Molavi
authors.affiliation: Department of Pathology, Shantou University Medical College, 22 Xinling Road, Shantou 515031, Guangdong Province, China. minsu@stu.edu.cn.
authors.forename: Min
authors.initials: M
authors.lastname: Su
authors.forename: Raymond
authors.initials: R
authors.lastname: Lai
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D015996:Survival Rate; D014158:Transcription, Genetic; D014410:Tumor Stem Cell Assay
chemical_list: D016328:NF-kappa B; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human