title: IL-6 expression predicts treatment response and outcome in squamous cell carcinoma of the esophagus.
abstract: BACKGROUND
  The identification of potential tumor markers can improve therapeutic planning and patient management. The aim of this study was to highlight the significance of IL-6 in esophageal squamous cell carcinoma (SCC).
  
  
  METHODS
  We retrospectively analyzed the clinical outcomes of 173 patients with esophageal SCC, and examined the correlation between IL-6 levels and clinical outcomes in esophageal cancer patients. Furthermore, the human esophageal SCC cell line CE81T was selected for cellular and animal experiments to investigate changes in tumor behavior and treatment response after manipulation of IL-6 expression.
  
  
  RESULTS
  In clinical outcome analysis, positive IL-6 staining and poor treatment response was significantly associated with shorter survival. Furthermore, the frequency of IL-6 immunoreactivity was significantly higher in esophageal cancer specimens than in non-malignant epithelium, and this staining was positively linked to the development of distant metastasis (p = 0.0003) and lower treatment response rates (p = 0.0001).By ELISA analysis, IL-6 serum levels were significantly elevated in patients developing disease failure.When IL-6 expression was inhibited, aggressive tumor behavior and radiation resistance could be overcome in vitro and in vivo. The underlying changes included increased cell death, less epithelial-mesenchymal transition and attenuated STAT3 activation. IL-6 inhibition was also associated with attenuated angiogenesis in tumor-bearing mice.
  
  
  CONCLUSIONS
  IL-6 was significantly associated with poor prognosis in patients with esophageal cancer. Targeting this cytokine could be a promising strategy for treatment of esophageal cancer, as evidenced by inhibition of aggressive tumor behavior and treatment resistance.
authors.affiliation: Department of Radiation Oncology, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan. miaofen@adm.cgmh.org.tw
authors.forename: Miao-Fen
authors.initials: MF
authors.lastname: Chen
authors.forename: Ping-Tsung
authors.initials: PT
authors.lastname: Chen
authors.forename: Ming Shian
authors.initials: MS
authors.lastname: Lu
authors.forename: Paul Yang
authors.initials: PY
authors.lastname: Lin
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Chen
authors.forename: Kuan-Der
authors.initials: KD
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D015870:Gene Expression; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D015850:Interleukin-6
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