Abstract
Dickkopf-related protein 1 (DKK1), an antagonist of the canonical Wnt pathway, has received tremendous attention over the past years as its dysregulation is said to be critically involved in a wide variety of gastrointestinal cancers. However, the potential clinical implications of DKK1 remain poorly understood. Although multimodal treatment options have been implemented over the past years, esophageal cancer (EC) patients still suffer from poor five-year overall survival rates ranging from 15% to 25%. Especially prognostic factors and biomarkers for risk stratification are lacking to choose the most beneficial treatment out of the emerging landscape of different treatment options. In this study, we analyzed the serum DKK1 (S-DKK1) levels of 91 EC patients prior to surgery in a single center study at the University Medical Center Hamburg-Eppendorf by enzyme-linked immunosorbent assay. High levels of S-DKK1 could be especially observed in patients suffering from esophageal adenocarcinoma which may promote the hypothesis of a crucial role of DKK1 in inflammation. S-DKK1 levels of ≥5800 pg/mL were shown to be associated with unfavorable five-year survival rates and the presence of CTCs. Interestingly, significantly lower S-DKK1 levels were detected in patients after neoadjuvant treatment, implying that S-DKK1 may serve as a useful biomarker for treatment monitoring. Multivariate analysis identified S-DKK1 as an independent prognostic marker with respect to overall survival in EC patients with a hazard ratio of 2.23. In conclusion, our data implicate a negative prognostic role of DKK1 with respect to the clinical outcome in EC patients. Further prospective studies should be conducted to implement S-DKK1 into the clinical routine for risk stratification and treatment monitoring.
Highlights
Esophageal cancer (EC) is a devastating malignant disease with half a million deaths per year worldwide [1]
As the use of serum Dickkopf-related protein 1 (DKK1) (S-DKK1) is limited to research and not yet established in the clinical setting, we determined the mean S-DKK1 of our 91 patients suffering from esophageal cancer (EC) and 30 obesity patients who served as the healthy control before surgery
We retrospectively analyzed the impact of S-DKK1 levels in 30 esophageal squamous cell cancer and 61 esophageal adenocarcinoma patients
Summary
Esophageal cancer (EC) is a devastating malignant disease with half a million deaths per year worldwide [1]. Esophageal adenocarcinoma (EAC), mainly dominate the histopathological landscape of esophageal tumors [2]. ESCC mostly develops in the proximal esophagus due to exposition to exogenous toxics including tobacco, alcohol and radiation. EAC develops as a metaplasia due to gastroesophageal reflux with subsequent development of dysplastic adenoma and transformation to malignant adenocarcinoma [2]. Curative treatment of EC includes surgery, chemotherapy and/or radiochemotherapy, either in a neoadjuvant or adjuvant treatment regimen. Despite the broad range of cytotoxic agents and the advances in surgery and radiotherapy, patients still have poor five-year overall survival (OS) rates of 15% to
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