Identification of a serum biomarker panel for the differential diagnosis of cholangiocarcinoma and primary sclerosing cholagnitis
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Published version
Author(s)
Type
Journal Article
Abstract
The non-invasive differentiation of malignant and benign biliary disease is a clinical challenge. Carbohydrate antigen 19-9 (CA19-9), leucine-rich α2-glycoprotein (LRG1), interleukin 6 (IL6), pyruvate kinase M2 (PKM2), cytokeratin 19 fragment (CYFRA21.1) and mucin 5AC (MUC5AC) have reported utility for differentiating cholangiocarcinoma (CCA) from benign biliary disease. Herein, serum levels of these markers were tested in 66 cases of CCA and 62 cases of primary sclerosing cholangitis (PSC) and compared with markers of liver function and inflammation. Markers panels were assessed for their ability to discriminate malignant and benign disease. Several of the markers were also assessed in pre-diagnosis biliary tract cancer (BTC) samples with performances evaluated at different times prior to diagnosis. We show that LRG1 and IL6 were unable to accurately distinguish CCA from PSC, whereas CA19-9, PKM2, CYFRA21.1 and MUC5AC were significantly elevated in malignancy. Area under the receiver operating characteristic curves for these individual markers ranged from 0.73–0.84, with the best single marker (PKM2) providing 61% sensitivity at 90% specificity. A panel combining PKM2, CYFRA21.1 and MUC5AC gave 76% sensitivity at 90% specificity, which increased to 82% sensitivity by adding gamma-glutamyltransferase (GGT). In the pre-diagnosis setting, LRG1, IL6 and PKM2 were poor predictors of BTC, whilst CA19-9 and C-reactive protein were elevated up to 2 years before diagnosis. In conclusion, LRG1, IL6 and PKM2 were not useful for early detection of BTC, whilst a model combining PKM2, CYFRA21.1, MUC5AC and GGT was beneficial in differentiating malignant from benign biliary disease, warranting validation in a prospective trial.
Date Issued
2018-04-03
Date Acceptance
2018-03-06
Citation
Oncotarget, 2018, 9, pp.17430-17442
ISSN
1949-2553
Publisher
Impact Journals
Start Page
17430
End Page
17442
Journal / Book Title
Oncotarget
Volume
9
Copyright Statement
© 2018 Cuenco et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY
3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Subjects
biliary tract cancer
cholangiocarcinoma
differential diagnosis
primary sclerosing cholangitis
serum biomarker
Publication Status
Published
OA Location
http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=24732&path%5B%5D=77576
Date Publish Online
2018-04-03