Department of Radiology, Kurume University School of Medicine and Center for Diagnostic Imaging, Kurume University Hospital, 67 Asahi-machi, Kurume 830-0011, Japan.
Oncol Rep. 2011 May;25(5):1211-6. doi: 10.3892/or.2011.1194. Epub 2011 Feb 23.
Differentiating intrahepatic cholangiocarcinoma (CCA) from other hepatic malignancies is crucial in deciding on treatment modalities and predicting clinical outcomes in patients. Periostin is a secreted protein from stromal cells and regulates the development of cancer cells through interaction with the extracellular matrix. Given that proliferation of fibrous stromal cells is a pathological feature of CCA, we examined the potential use of periostin as a serodiagnostic marker for this disease. Our study enrolled a total of 79 patients including liver cirrhosis (n=26), hepatocellular carcinoma (HCC, n=24), CCA (n=8), other hepatic malignancies (n=13) and histologically normal livers (normal control, n=8). Periostin expression was evaluated using immunohistochemistry and serum periostin level was determined via enzyme-linked immunoassay. The diagnostic performance of serum periostin levels for distinguishing CCA patients from others was also assessed. Strong expression of periostin was noted only in the fibrous stroma of CCA tissue. Serum periostin levels (median) were significantly higher in patients with CCA (513 ng/ml) compared to those patients with normal liver, liver cirrhosis, HCC and other malignancies (120, 146, 155, 213 ng/ml, respectively, all P<0.05). The area under receiver operating characteristics curve of serum periostin level was 0.94 [95% confidence interval (CI), 0.85-1.00, P<0.001]. With optimal cut-off value of 302 ng/ml, diagnostic performances for CCA were as follows: sensitivity, 0.88 (95% CI, 0.47-0.99); specificity, 0.92 (0.83-0.96); accuracy, 0.91 (0.83-0.96); positive predictive value, 0.54 (0.25-0.81); negative predictive value, 0.98 (0.92-0.99); positive-likelihood ratio, 10.4 (4.8-13.4); and negative-likelihood ratio, 0.13 (0.03-0.49). We demonstrated increased expression of periostin in the stroma of CCA tissue. Serum periostin levels were significantly elevated in patients with CCA and enable distinction between CCA and other hepatic malignancies.
区分肝内胆管癌（CCA）与其他肝脏恶性肿瘤对于确定治疗方式和预测患者临床结局至关重要。骨膜蛋白是一种来源于基质细胞的分泌蛋白，通过与细胞外基质相互作用来调节癌细胞的发育。鉴于纤维基质细胞的增殖是 CCA 的病理特征，我们研究了骨膜蛋白作为该疾病血清诊断标志物的潜在用途。本研究共纳入了 79 名患者，包括肝硬化（n=26）、肝细胞癌（HCC，n=24）、CCA（n=8）、其他肝脏恶性肿瘤（n=13）和组织学正常肝脏（正常对照组，n=8）。使用免疫组织化学评估骨膜蛋白的表达，通过酶联免疫吸附试验测定血清骨膜蛋白水平。还评估了血清骨膜蛋白水平区分 CCA 患者与其他患者的诊断性能。仅在 CCA 组织的纤维基质中观察到骨膜蛋白的强表达。CCA 患者的血清骨膜蛋白水平（中位数）明显高于正常肝、肝硬化、HCC 和其他恶性肿瘤患者（分别为 513、146、155、213 ng/ml，均 P<0.05）。血清骨膜蛋白水平的受试者工作特征曲线下面积为 0.94 [95%置信区间（CI），0.85-1.00，P<0.001]。当最佳截断值为 302 ng/ml 时，CCA 的诊断性能如下：敏感性为 0.88（95%CI，0.47-0.99）；特异性为 0.92（0.83-0.96）；准确性为 0.91（0.83-0.96）；阳性预测值为 0.54（0.25-0.81）；阴性预测值为 0.98（0.92-0.99）；阳性似然比为 10.4（4.8-13.4）；阴性似然比为 0.13（0.03-0.49）。我们证明了骨膜蛋白在 CCA 组织基质中的表达增加。CCA 患者的血清骨膜蛋白水平显著升高，可区分 CCA 与其他肝脏恶性肿瘤。
