Peptidase inhibitor 15 as a novel blood diagnostic marker for cholangiocarcinoma.

Background: We aimed to screen a specific secretory protein that could serve as blood diagnostic marker for cholangiocarcinoma (CCA).

Methods: Starting with the analysis of gene expression profiles in tumor tissues and matched normal tissues from cases with CCA and hepatocellular carcinoma (HCC), we identified peptidase inhibitor 15 (PI15) was a potential diagnostic marker for CCA. We demonstrated PI15 expression levels in CCA, HCC, and normal liver tissues. Furthermore, quantitative enzyme-linked immunosorbent assay (ELISA) assessed plasma PI15 levels in CCA (n = 61), HCC (n = 72), benign liver disease (n = 28), chronic hepatitis B (CHB) patients (n = 45), and healthy individuals (n = 45). The diagnostic value of PI15 was estimated by the area under the receiver operating characteristic (ROC) curve (AUC).

Findings: The positive rate of PI15 expression was 70% in CCA and only 9.1% in HCC; PI15 was not detected in normal liver tissue. High levels of plasma PI15 were evident in CCA patients, whereas only low levels were observed in cases involving HCC, benign liver disease, CHB patients, and healthy individuals. Plasma PI15 levels in CCA patients were obviously reduced (p = .0014) after surgery. The AUC of plasma PI15 for discriminating between CCA and HCC was 0.735. Furthermore, with a specificity of 94.44%, the combination of CA19-9 (>98.5 U/ml) and PI15 (>13 ng/ml) yielded a sensitivity of 80.39% for CCA and HCC.

Interpretation: PI15 exhibits promise as a novel marker for predicting the diagnosis and follow-up of CCA patients. FUND: Natural Science Research Foundation of Anhui Province and Natural Science Foundation of China.