| Ubiquitin-proteasome profiling for enhanced detection of hepatocellular carcinoma in patients with chronic liver disease. | |
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MedLine Citation:
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PMID: 21418304 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Background and Aim: A reliable test for the detection of hepatocellular carcinoma (HCC) could improve disease management. Recent reports suggested a link between abnormalities in the ubiquitin-proteasome system (UPS) and HCC. We investigated the potential of using UPS markers, along with HCC markers, to differentiate HCC from chronic liver disease (CLD). Methods: Sera from 135 HCC and 262 CLD patients were retrospectively analyzed for levels of UPS markers (proteasome, ubiquitin, and proteasome enzymatic activities) and the conventional HCC markers alpha fetoprotein (AFP), AFP-L3, and des-gamma-carboxyprothrombin (DCP). Multivariate logistic regression analysis was used to develop a model for differentiating HCC from CLD. The model was developed using a subset of 98 HCC patients and 104 CLD patients with advanced fibrosis or cirrhosis (Metavir F3-4) and then validated using an independent set (37 HCC and 44 CLD (F3-4)). Results: A UPS signature model incorporating six markers (trypsin-like, caspase-like, chymotrypsin-like, and normalized chymotrypsin-like activities of proteasomes; AFP; and DCP) accurately differentiated HCC from CLD (area under the curve = 0.938 [95% confidence interval, 0.884-0.991]). When analysis was restricted to patients with tumors ≤ 3 cm, the UPS model exhibited higher sensitivity (83.1% vs 51.8%) and specificity (90.2% vs 83.7%) than the three conventional markers, with good positive predictive values (34.2% vs 15.1%). These results were confirmed in the independent validation set. Conclusion: The UPS signature in combination with AFP and DCP provides sensitive and specific differentiation of HCC in patients with CLD. The importance of the UPS in HCC suggests that therapeutic approaches targeting the UPS should be explored. |
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Authors:
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Kevin Z Qu; Ke Zhang; Wanlong Ma; Hairong Li; Xiuqiang Wang; Xi Zhang; Francis Giles; Michelle Lai; Nezam H Afdhal; Maher Albitar |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of gastroenterology and hepatology Volume: 26 ISSN: 1440-1746 ISO Abbreviation: J. Gastroenterol. Hepatol. Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-03-22 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8607909 Medline TA: J Gastroenterol Hepatol Country: Australia |
Other Details:
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Languages: eng Pagination: 751-8 Citation Subset: IM |
Copyright Information:
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© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd. |
Affiliation:
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Quest Diagnostics Nichols Institute, San Juan Capistrano, California, USA the Cancer Therapy & Research Center at the University of Texas Health Science Center, San Antonio, Texas, USA Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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