title: 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.
authors.affiliation: Department of Radiology, Kurume University School of Medicine and Center for Diagnostic Imaging, Kurume University Hospital, 67 Asahi-machi, Kurume 830-0011, Japan. kimichan@med.kurume-u.ac.jp
authors.forename: Kiminori
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Takumi
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakashima
authors.forename: Junya
authors.initials: J
authors.lastname: Ono
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Ohta
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawaguchi
authors.forename: Tatsuyuki
authors.initials: T
authors.lastname: Tonan
authors.forename: Koichi
authors.initials: K
authors.lastname: Ohshima
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Yano
authors.forename: Naofumi
authors.initials: N
authors.lastname: Hayabuchi
authors.forename: Kenji
authors.initials: K
authors.lastname: Izuhara
authors.forename: Michio
authors.initials: M
authors.lastname: Sata
mesh_terms: D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D001653:Bile Ducts, Intrahepatic; D014408:Biomarkers, Tumor / Q000097:blood* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000097:blood* / Q000378:metabolism; D018281:Cholangiocarcinoma / Q000097:blood / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests
chemical_list: D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; C512835:POSTN protein, human