Assessment of serum concentrations of Dkk1 as potential biomarker for esophageal squamous cell carcinoma

Abstract

e15675 Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common fatal cancers worldwide due to the lack of an early disease screening strategy. Identification of diagnostic markers will greatly improve the morbid outcome. Dickkopf 1 (Dkk1) is a secreted antagonist of Wnt signaling pathway, an important pathway in tumorigenesis. The expressions of Dkk1 seem to be tumor-specific: reduced expressions have been seen in colorectal cancer, but elevated levels were reported for hepatoblastomas. In ESCC, the situation is less clear, for both elevation and reduction of Dkk1 were reported. The serum concentrations of Dkk1 have also been shown to be higher in ESCC patients’ sera in one study. In view of the varied outcome from Dkk1 tissue expressions and the scarce reports on Dkk1 serum concentration from ESCC patients, we therefore sought to determine the tissue expression and serum concentrations of Dkk1 as our first step to evaluate the potential of Dkk1 as a diagnostic marker for ESCC. Methods: The expression levels of Dkk1 in ten ESCC tumor and adjacent non-tumor tissues were examined by Western blot. Serum Dkk1 level of 168 samples were quantified in a double-blind fashion by ELISA (Dkk1 Duoset ELISA development kit from R & D Systems, Minneapolis, MN). To ensure that the serum Dkk1 detection was not affected by autoantibodies against Dkk1 present in sera, we also measured serum Dkk1 autoantibody levels by ELISA with modifications to the ELISA kit. Results: Seven out of ten of the tumors showed elevated Dkk1 level, while only two out of ten of the control normal tissue showed elevation. Surprisingly, after decoding of our serum samples into 80 patients and 88 normal controls, we found that Dkk1 level was significantly lower in patient sera (2.99ng/ml) than the normal samples (5.32ng/ml) (p=0.0001; t-test). The measurements were not obscured by the presence of Dkk1 autoantibodies, as they were not different between patient and control samples. Conclusions: Contrary to previous published results, we found Dkk1 is suppressed in patient sera, and thus our result undermines the potential of serum Dkk1 level as a predictive marker for ESCC. Further investigations will be needed to explain the discrepancies between the studies. No significant financial relationships to disclose.