Diagnostic Value of Autoantibodies against Ezrin in Esophageal Squamous Cell Carcinoma

Abstract

Esophageal squamous cell carcinoma (ESCC), one of the most common malignancies worldwide, is a highly aggressive and homogeneous entity occurring in esophageal squamous epithelium, and a reliable noninvasive test for early detection is needed. A recent study showed that serum autoantibodies against Ezrin could be detected in patients with pancreatic cancer. Here, we assessed whether autoantibodies against Ezrin could have diagnostic relevance for early ESCC. We analyzed autoantibodies against Ezrin in sera of 98 normal controls and 149 patients with ESCC. Ezrin autoantibodies levels were evaluated by enzyme-linked immunosorbent assay (ELISA). Results showed that higher levels of autoantibodies against Ezrin were observed in serum samples from patients with ESCC than in serum from normal controls (P < 0.0001). Based on a cutoff value of 0.319, the sensitivity and specificity of autoantibodies against Ezrin for diagnosis of ESCC were 27.5% and 95.9%, respectively. Compared with normal controls, the positive rate of autoantibodies against Ezrin was significantly elevated in patients with early-stage ESCC (P < 0.0001). Moreover, there was no significant difference of positivity of autoantibodies against Ezrin in ESCC patients categorized according to age, gender, tumor size, tumor invasion depth, tumor site, histological grade, lymph node status, or tumor stage. Our study indicates that the presence of autoantibodies against Ezrin is significantly associated with ESCC.

Figure 1

levels of serum Ezrin autoantibodies. (a) Median levels and interquartile ranges of serum Ezrin autoantibodies in ESCC patients and normal controls are illustrated by box plot and the whiskers show minimum and maximum value. (b) Scatter plots of OD values of Ezrin autoantibodies from sera of ESCC patients and normal controls. Black horizontal lines are means, and error bars are SEs. (c) Median levels and interquartile ranges of serum Ezrin autoantibodies in ESCC patients by AJCC stage are illustrated by box plot and the whiskers show minimum and maximum value. (d) Scatter plots of OD values of Ezrin autoantibodies from sera of ESCC patients by AJCC stage. Black horizontal lines are means, and error bars are SEs.

Figure 2

Western blotting analysis with representative sera recognizing Ezrin recombinant protein. The polyclonal anti-Ezrin antibody was used as positive control; lanes 1–5, five representative ESCC sera (with AJCC stage I, stage II, stage II, stage III, and stage III, resp.) with positive results in ELISA test have strong reactivity with Ezrin recombinant protein in western blotting analysis; lanes 6–10 are five representative normal control sera with negative reactivity.