iTRAQ reveals candidate pancreatic cancer serum biomarkers: influence of obstructive jaundice on their performance View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-04-11

AUTHORS

S Tonack, C Jenkinson, T Cox, V Elliott, R E Jenkins, N R Kitteringham, W Greenhalf, V Shaw, C W Michalski, H Friess, J P Neoptolemos, E Costello

ABSTRACT

Background:The aims of our study were to identify serum biomarkers that distinguish pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) patients from benign pancreatic disease patients and healthy subjects, and to assess the effects of jaundice on biomarker performance.Methods:Isobaric tags for relative and absolute quantification were used to compare pooled serum and pancreatic juice samples from a test set of 59 and 25 subjects, respectively. Validation was undertaken in 113 independent subjects.Results:Candidate proteins Complement C5, inter-α-trypsin inhibitor heavy chain H3, α1-β glycoprotein and polymeric immunoglobulin receptor were elevated in cancer, as were the reference markers CA19-9 and Reg3A. Biliary obstruction had a significant effect on the performance of the markers, in particular within the PDAC group where the presence of jaundice was associated with a significant increase in the levels of all six proteins (P<0.01). Consequently, in the absence of jaundice, proteins showed reduced sensitivity for PDAC patients over benign subjects and healthy controls (HCs). Similarly, in the presence of jaundice, markers showed reduced specificity for PDAC patients over benign subjects with jaundice. Combining markers enabled improved sensitivity for non-jaundiced PDAC patients over HCs and improved specificity for jaundiced PDAC patients over jaundiced benign disease subjects.Conclusions:The presence–absence of jaundice in the clinical scenario severely impacts the performance of biomarkers for PDAC diagnosis and has implications for their clinical translation. More... »

PAGES

1846-1853

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/bjc.2013.150

DOI

http://dx.doi.org/10.1038/bjc.2013.150

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1048271791

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/23579209


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31 schema:description Background:The aims of our study were to identify serum biomarkers that distinguish pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) patients from benign pancreatic disease patients and healthy subjects, and to assess the effects of jaundice on biomarker performance.Methods:Isobaric tags for relative and absolute quantification were used to compare pooled serum and pancreatic juice samples from a test set of 59 and 25 subjects, respectively. Validation was undertaken in 113 independent subjects.Results:Candidate proteins Complement C5, inter-α-trypsin inhibitor heavy chain H3, α1-β glycoprotein and polymeric immunoglobulin receptor were elevated in cancer, as were the reference markers CA19-9 and Reg3A. Biliary obstruction had a significant effect on the performance of the markers, in particular within the PDAC group where the presence of jaundice was associated with a significant increase in the levels of all six proteins (P<0.01). Consequently, in the absence of jaundice, proteins showed reduced sensitivity for PDAC patients over benign subjects and healthy controls (HCs). Similarly, in the presence of jaundice, markers showed reduced specificity for PDAC patients over benign subjects with jaundice. Combining markers enabled improved sensitivity for non-jaundiced PDAC patients over HCs and improved specificity for jaundiced PDAC patients over jaundiced benign disease subjects.Conclusions:The presence–absence of jaundice in the clinical scenario severely impacts the performance of biomarkers for PDAC diagnosis and has implications for their clinical translation.
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39 H3
40 PDAC diagnosis
41 PDAC group
42 PDAC patients
43 absence
44 absence of jaundice
45 absolute quantification
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47 benign pancreatic disease patients
48 benign subjects
49 biliary obstruction
50 biomarker performance
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52 cancer
53 cancer patients
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57 complement C5
58 control
59 diagnosis
60 disease patients
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62 effect
63 effects of jaundice
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67 iTRAQ
68 immunoglobulin receptor
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72 increase
73 independent subjects
74 influence
75 inhibitor heavy chain H3
76 isobaric tags
77 jaundice
78 juice samples
79 levels
80 markers
81 obstruction
82 obstructive jaundice
83 pancreatic cancer patients
84 pancreatic disease patients
85 pancreatic juice samples
86 patients
87 performance
88 performance of biomarkers
89 polymeric immunoglobulin receptor
90 presence
91 presence of jaundice
92 protein
93 quantification
94 receptors
95 reduced sensitivity
96 reduced specificity
97 samples
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101 set
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