To Predict the Responses of Esophageal Cancer to Preoperative Chemoradiotherapy and Prognosis by Molecular Markers----The Role of UCP

  • Chen, Miao-fen (PI)
  • Chen, Chih-cheng (CoPI)
  • Chen, Wen-Cheng (CoPI)
  • Wu, Chun Te (CoPI)

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details

Abstract

The prognosis of patients with esophageal cancer is poor. Recent evidence strongly suggests that neoadjuvant chemoradiotherapy (CCRT) improves outcome, and this has become a standard treatment option. 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. We therefore used a high- sensitive colormetric membrane array method to examine the role of important predictors in esophageal cancer. According to our previous data (accepted in J Mol. Med), UCP might be a promising predictor of esophageal squamous cell carcinoma by membrane array 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. By the data of 25-gene membrane array analysis, UCP was the only factor significantly associated with the extent of tumor burden in esophageal cancer patients. Our immunochemistry findings further indicate that UCP positivity was linked to poor response to neoadjuvant therapy and worse survival. In cell culture, inhibited UCP significantly decrease tumor growth and the capacity for metastasis. Furthermore, the epithelial-mesenchymal transition (EMT) induced by VHL/HIF-1α-TGF-β1 pathway might be the underlying mechanism responsible to the more aggressive tumor growth in UCP-positive esophageal cancer. Although our previous results suggest that UCP is a promising predictor for esophageal cancer, the number of enrolled cases was limited and lacked strongly statistic significance. Therefore, the first aim in the study is to collect more samples from patients with esophageal cancer, and analyze by high-throughput membrane array-based multimarker assay. The second aim is to evaluate the role of UCP in vivo experiments, because further characterization of the effects of UCP in in vivo models and the mechanisms underlying treatment response will help to clarify its role and its potential as a molecular target for therapeutic intervention in esophageal cancer. How to overcome treatment resistance in UCP overexpressed tumor remains another important issue in esophageal cancer manipulation. Combination targeted therapy should be opportunities. Thus, we sough to investigate the mechanisms responsible to the resistance of esophageal cancer. Moreover, modulation of resistance pathway or combination with other targeted therapy (including proteasome inhibitor and mTOR inhibitor) could potentially result in higher response rates to treatment in patients with esophageal cancer.Hope these results may provide a new direction for therapeutic approach

Project IDs

Project ID:PC9902-1694
External Project ID:NSC98-2314-B182-038-MY2
StatusFinished
Effective start/end date01/08/1031/07/11

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