Xu Fenghuang, Yi Junzhu, Wang Feifei, Wang Weiwei, Wang Zhuoya, Xue Jiangnan, Luan Xiying
Department of Immunology, Binzhou Medical University, Yantai, Shandong 264003, P.R. China.
Department of Anesthesiology, The Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264100, P.R. China.
Oncol Lett. 2017 Dec;14(6):8138-8143. doi: 10.3892/ol.2017.7215. Epub 2017 Oct 18.
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.
先前的研究表明，B7-H3以及炎性细胞因子白细胞介素（IL）-17、IL-8和IL-6参与了多种肿瘤的发生发展。本研究的目的是：i）研究可溶性B7-H3（sB7-H3）与肝细胞癌（HCC）患者血清中IL-17、IL-8和IL-6细胞因子水平之间的关联；ii）确定它们在HCC诊断中的潜在价值。采用酶联免疫吸附测定法（ELISA）检测HCC患者和健康对照者血清中的sB7-H3、IL-17、IL-8和IL-6水平。使用受试者工作特征曲线和曲线下面积（AUC）比较这些生物标志物在HCC诊断中的准确性。采用逻辑回归模型研究联合检测sB7-H3、IL-17、IL-8和IL-6水平评估HCC诊断的准确性。数据表明，与健康对照组相比，HCC患者血清中的sB7-H3、IL-17、IL-8和IL-6水平显著升高。血清sB7-H3水平与血清IL-17呈正相关，而血清IL-8水平与血清IL-17水平呈负相关。sB7-H3、IL-17、IL-8和IL-6的AUC值分别为83.2%、65.7%、95.3%和97.0%，表明这四种生物标志物在诊断HCC方面均具有统计学意义上的显著能力。使用逻辑回归模型，四种生物标志物联合检测的AUC值、敏感性和特异性分别为99.2%、96.67%和97.14%。这显著高于在逻辑回归模型中单独使用任何一种生物标志物评估其在HCC诊断中的准确性时所达到的值。回归模型中sB7-H3、IL-17、IL-8和IL-6联合预测概率的最佳截断值为0.5745。总之，本研究表明HCC患者血清sB7-H3和IL-17水平之间存在正相关。联合检测血清sB7-H3、IL-17、IL-8和IL-6水平在HCC诊断中具有很大的应用潜力。
