Role of IL-6/Stat3 Signaling and Myeloid Derived Suppressor Cells in the Prognosis of Esophageal Cancer

The prognosis of patients with esophageal cancer is poor. Early identification of patients who will respond to CCRT would allow us to maximize therapeutic benefit and minimize treatment-induced toxicity. Despite attempts to develop new technologies for early screening of esophageal cancer and to identify factors that will predict responses to neoadjuvant CCRT, no suitable markers have been identified to date. According to our previous data, UCP might be a promising predictor of esophageal squamous cell carcinoma by 25-gene membrane array analysis and immunochemical staining analysis. E2-EPF ubiquitin carrier protein (UCP), a 24-kDa protein, is a member of the E2 family, which, together with an E1 and an E3, catalyzes the addition of ubiquitin to proteins. UCP was the factor significantly associated with the extent of tumor burden in esophageal cancer patients, and the positivity was linked to poor response to neoadjuvant therapy and worse survival. Furthermore, by cellular experiments the epithelial-mesenchymal transition (EMT) induced by VHL/HIF- 1a-TGF-pi pathway might be the underlying mechanism responsible to the more aggressive tumor growth in UCP-positive esophageal cancer. In the following research, we found that IL-ip is a significant predictor of prognosis. The increased UCP and subsequent EMT-related changes mediated by the activation of NF-kB might be responsible to the predictive role of IL-ip in esophageal SCC. We also demonstrated that DNMT3b is significantly linked to poor prognosis for patients with esophageal cancer, as evidenced related to aggressive tumor behavior and treatment resistance. Epidemiologic and experimental evidence supports the concept that chronic inflammation promotes the development and progression of cancers. The main cytokines in humans include IL-6 and IL-ip. IL-6 is the main inducer, and IL-ip can induce IL-6 production from tumor cells and host cells. IL-6 signaling is implicated in the regulation of tumor growth and metastatic spread, and its level could be correlated with a poor prognosis in different cancers. Recent evidence supports a positive link between the activation of IL-6/STAT3 signaling, and epigenetic gene silencing is promoted by DNMT in some types of malignancy. Furthermore, Myeloid-derived suppressor cells (MDSC), was reported to markedly expand in tumor-bearing mice and patients with cancer, and contribute to an immunosuppressive tumor microenvironment. The induction, expansion, and retention of MDSC are due to several different factors, including potent inflammatory mediators, such as IL-6. Therefore, we aimed to investigate the role of IL-6/stat3 signaling and MDSC in the prognosis of esophageal cancer by immunochemical staining, ELISA analysis, and flow cytometry analysis in addition to cellular and animal experiments. Hope these results may provide a new direction for therapeutic approach

Project ID:PC10301-0544
External Project ID:NSC102-2314-B182-052-MY3