The Early Diagnostic Value of Serum Interleukin-8 in Esophagogastric Junction Adenocarcinoma

Abstract

Background: Esophagogastric junction adenocarcinoma (EJA) is one of the most common malignant tumors of digestive tract with high mortality worldwide. Given a lack of early diagnosis biomarkers, the prognosis of EJA is poor. Non-invasive biomarkers for early-stage EJA are urgently required.

Objective: We aimed at evaluating the early diagnostic value of serum interleukin-8 (IL-8) level in EJA patients.

Methods: The IL-8 mRNA expression data were analyzed based on the stomach cardia adenocarcinoma samples of The Cancer Genome Atlas (TCGA) database. Enzyme-linked immunosorbent assay (ELISA) was used to measure the concentration of serum IL-8 in 95 EJA patients and 95 normal controls enrolled from 2 different cancer hospitals. The diagnostic accuracy of serum IL-8 was evaluated by applying Mann-Whitney U test and receiver operating characteristic (ROC) curve.

Results: The mRNA expression levels and serum levels of IL-8 in EJA group were significantly higher than those in the normal group (all P < 0.001). The areas under the ROC curve (AUC) were 0.661 (95% CI, 0.583-0.740) and 0.745 (95% CI, 0.606-0.885), with the sensitivities of 43.2% (95% CI, 33.2%-53.7%) and 66.7% (95% CI, 46.0%-82.8%) and the specificities of 87.4% (95% CI, 78.6%-93.1%) in EJA group and early-EJA group, respectively, when the optimal cutoff value was 109.086 pg/mL. The clinical data analysis showed there were significant correlations between patient genders, depth of invasion, lymph node metastasis, TNM stage and the serum level of IL-8 (all P < 0.05).

Conclusions: Serum IL-8 represents a potential diagnostic biomarker to identify early-stage EJA.

Keywords: ROC; biomarker; diagnosis; esophagogastric junction adenocarcinoma; interleukin-8; serum.

Figure 1.

IL-8 expression level in STAD and normal tissue from TCGA database. Box plot illustrates the visualization of interquartile range including minimum, 25th percentile, median, 75th percentile and maximum values of IL-8 in cardia adenocarcinoma tissue and non-cardia adenocarcinoma tissue of STAD, and normal tissue. T test shows significant difference when the 2 groups are compared with the normal group respectively. The difference of IL-8 expression was not significant between cardia adenocarcinoma and non-cardia adenocarcinoma. IL-8, interleukin-8; STAD, stomach adenocarcinoma. (***Mean P < 0.001).

Figure 2.

Serum IL-8 level in EJA and normal controls. (A) The EJA group is in red and the normal controls group is in blue. The sample counts on higher concentration in EJA group are more than those of normal controls. (B) Box plot elucidates median level and interquartile ranges, and the whiskers show minimum and maximum value of serum IL-8 in EJA patients and normal controls. (C) Scatter plots show the serum IL-8 level from EJA patients and normal controls. Black horizontal lines are mean, and error bars are SEs. Mann-Whitney U test was executed to verify the statistics differences. IL-8, interleukin-8; EJA, esophagogastric junction adenocarcinoma. (***Mean P < 0.001).

Figure 3.

ROC curve analysis of serum IL-8 in EJA and early-stage EJA. ROC curve of EJA groups and normal controls group is in red and blue, respectively. The area under the black diagonal line is 0.5 for reference. EJA, esophagogastric junction adenocarcinoma; ROC curve, receiver operating characteristic curve.