Periostin, a matrix protein, has potential as a novel serodiagnostic marker for cholangiocarcinoma

Abstract

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.