Abstract
Previous studies have demonstrated that B7-H3, and the inflammatory cytokines interleukin (IL)-17, IL-8 and IL-6, are involved in the development of a variety of tumors. The objectives of the present study were: i) To investigate the association between soluble B7-H3 (sB7-H3) and cytokine levels of IL-17, IL-8 and IL-6 in the serum of patients with hepatocellular carcinoma (HCC); and ii) to determine their potential value for use in HCC diagnosis. Serum sB7-H3, IL-17, IL-8 and IL-6 levels in the HCC patients and healthy control subjects were measured using ELISA. The accuracy of each of these biomarkers in HCC diagnosis was compared using a receiver operating characteristic curve and the area under the curve (AUC). A logistic regression model was used to investigate the accuracy of diagnosing HCC when evaluated using combined determinations of sB7-H3, IL-17, IL-8 and IL-6 levels. The data demonstrated that serum levels of sB7-H3, IL-17, IL-8 and IL-6 were significantly increased in HCC patients compared with those in the healthy control group. Serum sB7-H3 levels were positively associated with serum IL-17, whereas serum IL-8 levels were negatively correlated with serum IL-17 levels. The AUC values for sB7-H3, IL-17, IL-8 and IL-6 were 83.2, 65.7, 95.3 and 97.0%, respectively, and indicated that all four biomarkers exhibited a statistically significant capacity for diagnosing HCC. Using the logistic regression model, the AUC value, sensitivity and specificity, as determined for the combination of the four biomarkers, were 99.2, 96.67 and 97.14%, respectively. This was significantly greater than that achieved when any single biomarker was used alone in the logistic regression model to assess their accuracy in HCC diagnosis. The optimum cutoff value of the predicted probability obtained by the combination of sB7-H3, IL-17, IL-8 and IL-6 in the regression model was 0.5745. To conclude, the present study revealed that there exists a positive association between serum sB7-H3 and IL-17 levels in HCC patients. Determinations involving the combination of serum sB7-H3, IL-17, IL-8 and IL-6 levels demonstrate great potential for use in HCC diagnosis.