Angiopoietin-2 and biliary diseases: elevated serum, but not bile levels are associated with cholangiocarcinoma
The diagnosis of cholangiocarcinoma (CC) is challenging especially in patients with primary sclerosing cholangitis (PSC) and often delayed due to the lack of reliable markers. Angiopoietin-2 (Angpt-2) has been employed as a biomarker of angiogenesis and might be involved in tumor neoangiogenesis. To...
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| creator | Voigtländer, Torsten David, Sascha Thamm, Kristina Schlué, Jerome Metzger, Jochen Manns, Michael P Lankisch, Tim O |
| description | The diagnosis of cholangiocarcinoma (CC) is challenging especially in patients with primary sclerosing cholangitis (PSC) and often delayed due to the lack of reliable markers. Angiopoietin-2 (Angpt-2) has been employed as a biomarker of angiogenesis and might be involved in tumor neoangiogenesis.
To evaluate the diagnostic potential of Angpt-2 as a biomarker to detect patients with CC.
Bile and serum Angpt-2 levels were measured in patients with CC (n=45), PSC (n=74), CC complicating PSC (CC/PSC) (n=11) and patients with bile duct stones (n=37) in a cross sectional study. Diagnostic accuracy of Angpt-2 was compared to carbohydrate antigen 19-9 (CA19-9). Fluorescent immunohistochemistry from human CC liver tissue samples was performed to localize the origin of Angpt-2.
Serum Angpt-2 concentration was significantly elevated in patients with CC compared to control patients (p |
| doi_str_mv | 10.1371/journal.pone.0097046 |
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To evaluate the diagnostic potential of Angpt-2 as a biomarker to detect patients with CC.
Bile and serum Angpt-2 levels were measured in patients with CC (n=45), PSC (n=74), CC complicating PSC (CC/PSC) (n=11) and patients with bile duct stones (n=37) in a cross sectional study. Diagnostic accuracy of Angpt-2 was compared to carbohydrate antigen 19-9 (CA19-9). Fluorescent immunohistochemistry from human CC liver tissue samples was performed to localize the origin of Angpt-2.
Serum Angpt-2 concentration was significantly elevated in patients with CC compared to control patients (p<0.05). Diagnostic accuracy of Angpt-2 as determined by receiver operating characteristic (ROC) analysis resulted in a higher area under the curve (AUC) value compared to CA19-9 (AUC: 0.85 versus 0.77; 95% confidence interval (CI): 0.74-0.93 versus 0.65-0.87, respectively). Angpt-2 was also detectable in bile, but was not associated with the presence of CC. Immunohistochemistry revealed a strong induction of Angpt-2 expression in the tumor vasculature.
Circulating Angpt-2 in serum might be a promising protein candidate locally derived from the tumor vasculature in patients with CC. Measurement of Angpt-2 in serum may be useful for diagnosis and further clinical management of patients with CC.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0097046</identifier><identifier>PMID: 24823366</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Accuracy ; Angiogenesis ; Angiopoietin ; Angiopoietin-2 - blood ; Angiopoietin-2 - metabolism ; Bile ; Bile - metabolism ; Bile ducts ; Biomarkers ; Biomarkers, Tumor - blood ; Carbohydrates ; Cholangiocarcinoma ; Cholangiocarcinoma - blood ; Cholangiocarcinoma - diagnosis ; Cholangitis ; Cohort Studies ; Confidence intervals ; Cross-Sectional Studies ; Diagnosis ; Diagnostic systems ; Endocrinology ; Endoscopy ; Fluorescence ; Gallbladder diseases ; Gastroenterology ; Hepatology ; Humans ; Hypertension ; Immunohistochemistry ; Laboratories ; Liver ; Liver cancer ; Medical diagnosis ; Medical prognosis ; Medical schools ; Medicine and Health Sciences ; Nephrology ; Pathogenesis ; Patients ; R&D ; Research & development ; Statistics, Nonparametric ; Ultrasonic imaging ; Vascular endothelial growth factor</subject><ispartof>PloS one, 2014-05, Vol.9 (5), p.e97046-e97046</ispartof><rights>2014 Voigtländer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Voigtländer et al 2014 Voigtländer et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-b175e07f9c200535e87f024b7b8c67d46e846ce4b636783e0a7b4acc90df2c323</citedby><cites>FETCH-LOGICAL-c526t-b175e07f9c200535e87f024b7b8c67d46e846ce4b636783e0a7b4acc90df2c323</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4019663/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4019663/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53770,53772,79347,79348</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24823366$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Björkström, Niklas K.</contributor><creatorcontrib>Voigtländer, Torsten</creatorcontrib><creatorcontrib>David, Sascha</creatorcontrib><creatorcontrib>Thamm, Kristina</creatorcontrib><creatorcontrib>Schlué, Jerome</creatorcontrib><creatorcontrib>Metzger, Jochen</creatorcontrib><creatorcontrib>Manns, Michael P</creatorcontrib><creatorcontrib>Lankisch, Tim O</creatorcontrib><title>Angiopoietin-2 and biliary diseases: elevated serum, but not bile levels are associated with cholangiocarcinoma</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The diagnosis of cholangiocarcinoma (CC) is challenging especially in patients with primary sclerosing cholangitis (PSC) and often delayed due to the lack of reliable markers. Angiopoietin-2 (Angpt-2) has been employed as a biomarker of angiogenesis and might be involved in tumor neoangiogenesis.
To evaluate the diagnostic potential of Angpt-2 as a biomarker to detect patients with CC.
Bile and serum Angpt-2 levels were measured in patients with CC (n=45), PSC (n=74), CC complicating PSC (CC/PSC) (n=11) and patients with bile duct stones (n=37) in a cross sectional study. Diagnostic accuracy of Angpt-2 was compared to carbohydrate antigen 19-9 (CA19-9). Fluorescent immunohistochemistry from human CC liver tissue samples was performed to localize the origin of Angpt-2.
Serum Angpt-2 concentration was significantly elevated in patients with CC compared to control patients (p<0.05). Diagnostic accuracy of Angpt-2 as determined by receiver operating characteristic (ROC) analysis resulted in a higher area under the curve (AUC) value compared to CA19-9 (AUC: 0.85 versus 0.77; 95% confidence interval (CI): 0.74-0.93 versus 0.65-0.87, respectively). Angpt-2 was also detectable in bile, but was not associated with the presence of CC. Immunohistochemistry revealed a strong induction of Angpt-2 expression in the tumor vasculature.
Circulating Angpt-2 in serum might be a promising protein candidate locally derived from the tumor vasculature in patients with CC. Measurement of Angpt-2 in serum may be useful for diagnosis and further clinical management of patients with CC.</description><subject>Accuracy</subject><subject>Angiogenesis</subject><subject>Angiopoietin</subject><subject>Angiopoietin-2 - blood</subject><subject>Angiopoietin-2 - metabolism</subject><subject>Bile</subject><subject>Bile - metabolism</subject><subject>Bile ducts</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - blood</subject><subject>Carbohydrates</subject><subject>Cholangiocarcinoma</subject><subject>Cholangiocarcinoma - blood</subject><subject>Cholangiocarcinoma - diagnosis</subject><subject>Cholangitis</subject><subject>Cohort Studies</subject><subject>Confidence intervals</subject><subject>Cross-Sectional Studies</subject><subject>Diagnosis</subject><subject>Diagnostic systems</subject><subject>Endocrinology</subject><subject>Endoscopy</subject><subject>Fluorescence</subject><subject>Gallbladder diseases</subject><subject>Gastroenterology</subject><subject>Hepatology</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Immunohistochemistry</subject><subject>Laboratories</subject><subject>Liver</subject><subject>Liver cancer</subject><subject>Medical diagnosis</subject><subject>Medical prognosis</subject><subject>Medical schools</subject><subject>Medicine and Health Sciences</subject><subject>Nephrology</subject><subject>Pathogenesis</subject><subject>Patients</subject><subject>R&D</subject><subject>Research & development</subject><subject>Statistics, Nonparametric</subject><subject>Ultrasonic imaging</subject><subject>Vascular endothelial growth 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and biliary diseases: elevated serum, but not bile levels are associated with cholangiocarcinoma</title><author>Voigtländer, Torsten ; David, Sascha ; Thamm, Kristina ; Schlué, Jerome ; Metzger, Jochen ; Manns, Michael P ; Lankisch, Tim O</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-b175e07f9c200535e87f024b7b8c67d46e846ce4b636783e0a7b4acc90df2c323</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Accuracy</topic><topic>Angiogenesis</topic><topic>Angiopoietin</topic><topic>Angiopoietin-2 - blood</topic><topic>Angiopoietin-2 - metabolism</topic><topic>Bile</topic><topic>Bile - metabolism</topic><topic>Bile ducts</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - blood</topic><topic>Carbohydrates</topic><topic>Cholangiocarcinoma</topic><topic>Cholangiocarcinoma - blood</topic><topic>Cholangiocarcinoma - diagnosis</topic><topic>Cholangitis</topic><topic>Cohort 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Sascha</au><au>Thamm, Kristina</au><au>Schlué, Jerome</au><au>Metzger, Jochen</au><au>Manns, Michael P</au><au>Lankisch, Tim O</au><au>Björkström, Niklas K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Angiopoietin-2 and biliary diseases: elevated serum, but not bile levels are associated with cholangiocarcinoma</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-05-13</date><risdate>2014</risdate><volume>9</volume><issue>5</issue><spage>e97046</spage><epage>e97046</epage><pages>e97046-e97046</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The diagnosis of cholangiocarcinoma (CC) is challenging especially in patients with primary sclerosing cholangitis (PSC) and often delayed due to the lack of reliable markers. Angiopoietin-2 (Angpt-2) has been employed as a biomarker of angiogenesis and might be involved in tumor neoangiogenesis.
To evaluate the diagnostic potential of Angpt-2 as a biomarker to detect patients with CC.
Bile and serum Angpt-2 levels were measured in patients with CC (n=45), PSC (n=74), CC complicating PSC (CC/PSC) (n=11) and patients with bile duct stones (n=37) in a cross sectional study. Diagnostic accuracy of Angpt-2 was compared to carbohydrate antigen 19-9 (CA19-9). Fluorescent immunohistochemistry from human CC liver tissue samples was performed to localize the origin of Angpt-2.
Serum Angpt-2 concentration was significantly elevated in patients with CC compared to control patients (p<0.05). Diagnostic accuracy of Angpt-2 as determined by receiver operating characteristic (ROC) analysis resulted in a higher area under the curve (AUC) value compared to CA19-9 (AUC: 0.85 versus 0.77; 95% confidence interval (CI): 0.74-0.93 versus 0.65-0.87, respectively). Angpt-2 was also detectable in bile, but was not associated with the presence of CC. Immunohistochemistry revealed a strong induction of Angpt-2 expression in the tumor vasculature.
Circulating Angpt-2 in serum might be a promising protein candidate locally derived from the tumor vasculature in patients with CC. Measurement of Angpt-2 in serum may be useful for diagnosis and further clinical management of patients with CC.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24823366</pmid><doi>10.1371/journal.pone.0097046</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Accuracy Angiogenesis Angiopoietin Angiopoietin-2 - blood Angiopoietin-2 - metabolism Bile Bile - metabolism Bile ducts Biomarkers Biomarkers, Tumor - blood Carbohydrates Cholangiocarcinoma Cholangiocarcinoma - blood Cholangiocarcinoma - diagnosis Cholangitis Cohort Studies Confidence intervals Cross-Sectional Studies Diagnosis Diagnostic systems Endocrinology Endoscopy Fluorescence Gallbladder diseases Gastroenterology Hepatology Humans Hypertension Immunohistochemistry Laboratories Liver Liver cancer Medical diagnosis Medical prognosis Medical schools Medicine and Health Sciences Nephrology Pathogenesis Patients R&D Research & development Statistics, Nonparametric Ultrasonic imaging Vascular endothelial growth factor |
| title | Angiopoietin-2 and biliary diseases: elevated serum, but not bile levels are associated with cholangiocarcinoma |
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