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

ABSTRACT: 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.

SUBMITTER: Jiang Y

PROVIDER: S-EPMC6414306 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

Jiang Yong Y Zheng Xiaohu X Jiao Defeng D Chen Peng P Xu Yechuan Y Wei Haiming H Qian Yeben Y

EBioMedicine 20190109

<h4>Background</h4>We aimed to screen a specific secretory protein that could serve as blood diagnostic marker for cholangiocarcinoma (CCA).<h4>Methods</h4>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, quantitativ ...[more]

PMID: 30638862

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Project description:Growth differentiation factor 15 (GDF15) has been reported to be associated with fibrosis and cancer in liver disease. Diagnosis of autoimmune hepatitis (AIH) is often difficult because of the lack of specific markers. We investigated whether GDF15 is useful for diagnosing AIH and determined its therapeutic effects. We enrolled 171 Japanese patients as follows: AIH (n = 45), hepatitis B (HB) (n = 17), hepatitis C (HC) (n = 15), primary biliary cholangitis (PBC) (n = 20), and 74 healthy controls. Serum GDF15 levels were measured, and immunohistological analyses of GDF15 were performed using liver tissue of AIH patients. (1) GDF15 levels (pg/ml) were higher in AIH (1994.3 ± 1258.0) and HC (1568.0 ± 822.3) than in HB (953.2 ± 871.4), PBC (643.9 ± 247.0), and controls (475.3 ± 145.3) (p < 0.0001), as well as in cirrhosis patients (n = 31) than in non-cirrhosis patients (n = 66) (1926.6 ± 1026.0 vs. 1249.1 ± 1124.1, p < 0.0001). In non-cirrhosis patients, GDF15 levels were higher in AIH (1914.0 ± 1327.2) than in HC (955.7 ± 502.7), HB (519.3 ± 197.5), and PBC (643.9 ± 247.0) (p < 0.0001). (2) GDF15 was positively correlated with M2BPGi (r = 0.7728), total bilirubin (r = 0.6231), and PT-INR (r = 0.6332). (3) GDF15 levels could be used to distinguish AIH from other liver diseases in non-cirrhosis patients, with an area under the curve of 0.9373 (sensitivity 93.6%, specificity 79.3%, cut-off value 931.3). (4) GDF15 in AIH decreased after treatment. (5) Immunohistological analyses in AIH liver tissues revealed that GDF15 was strongly expressed in inflammatory cells, hepatic cytoplasm, and sinusoidal endothelial cells, but decreased after treatment. GDF15 is a novel diagnostic marker for AIH and is also expected to be a therapeutic marker for AIH.Clinical Trials Registration: The study protocol was approved by the institutional review board of Kurume University (Approval No.: 19049).

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

Publications

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

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