IL-6 expression predicts treatment response and outcome in squamous cell carcinoma of the esophagus

Miao Fen Chen, Ping Tsung Chen, Ming Shian Lu, Paul Yang Lin, Wen Cheng Chen, Kuan Der Lee

Research output: Contribution to journalArticle

59 Citations (Scopus)

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.

Original languageEnglish
Article number26
JournalMolecular Cancer
Volume12
Issue number1
DOIs
Publication statusPublished - Apr 5 2013
Externally publishedYes

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Esophagus
Squamous Cell Carcinoma
Interleukin-6
Esophageal Neoplasms
Neoplasms
Therapeutics
Staining and Labeling
Epithelial-Mesenchymal Transition
Tumor Biomarkers
Cell Death
Epithelium
Enzyme-Linked Immunosorbent Assay
Radiation
Cytokines
Neoplasm Metastasis
Cell Line
Survival
Serum
Esophageal Squamous Cell Carcinoma

Keywords

  • IL-6, Esophageal squamous cell carcinoma
  • Prognosis

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Oncology

Cite this

IL-6 expression predicts treatment response and outcome in squamous cell carcinoma of the esophagus. / Chen, Miao Fen; Chen, Ping Tsung; Lu, Ming Shian; Lin, Paul Yang; Chen, Wen Cheng; Lee, Kuan Der.

In: Molecular Cancer, Vol. 12, No. 1, 26, 05.04.2013.

Research output: Contribution to journalArticle

Chen, Miao Fen ; Chen, Ping Tsung ; Lu, Ming Shian ; Lin, Paul Yang ; Chen, Wen Cheng ; Lee, Kuan Der. / IL-6 expression predicts treatment response and outcome in squamous cell carcinoma of the esophagus. In: Molecular Cancer. 2013 ; Vol. 12, No. 1.
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