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

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

doi:10.1186/1476-4598-12-26

Abstract

BackgroundThe 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).MethodsWe 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.ResultsIn 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.ConclusionsIL-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.

Highlights

The identification of potential tumor markers can improve therapeutic planning and patient management
Evidence suggests that IL-6 is a critical factor in a variety of malignancies [11,13,14], how IL-6 modulates the biological activities of esophageal carcinoma cells and how it is associated with the prognosis of esophageal cancer remains unclear
Level of IL-6 in esophageal squamous cell carcinoma (SCC) The Immunohistochemical staining (IHC) data for tissue microarray (TMA) slides demonstrated that IL-6 was overexpressed in tumor tissues compared to adjacent non-malignant epithelial tissues (Figure 1a)

Summary

Introduction

The identification of potential tumor markers can improve therapeutic planning and patient management. Despite improvements in its detection and management, the prognosis in patients with esophageal cancer remains poor, with a 5-year survival of 15–34% [1,2]. Increased IL-6 serum levels were reported to be associated with metastasis and poor prognosis in prostate, ovarian and gastrointestinal cancers [10,11,12]. Evidence suggests that IL-6 is a critical factor in a variety of malignancies [11,13,14], how IL-6 modulates the biological activities of esophageal carcinoma cells and how it is associated with the prognosis of esophageal cancer remains unclear. There are two distinct histological types of esophageal cancer: squamous cell carcinoma (SCC) and adenocarcinoma. We investigated the role of IL-6 in esophageal SCC in vitro and in vivo, and examined the correlation between IL-6 levels and clinical outcomes in esophageal cancer patients

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