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

• Published in: British journal of cancer Vol. 108; no. 9; pp. 1846 - 1853
• Main Authors: Tonack, S, Jenkinson, C, Cox, T, Elliott, V, Jenkins, R E, Kitteringham, N R, Greenhalf, W, Shaw, V, Michalski, C W, Friess, H, Neoptolemos, J P, Costello, E
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.05.2013; Nature Publishing Group
• Subjects: 692/53/2421; 692/699/1503/1712; 692/699/67/1504/1713; Aged; Alpha-Globulins - analysis; Antigens, Neoplasm - blood; Biological and medical sciences; Biomarkers, Tumor - blood; Biomedical and Life Sciences; Biomedicine; CA-19-9 Antigen - blood; Cancer Research; Complement C5 - analysis; Drug Resistance; Epidemiology; Female; Gastroenterology. Liver. Pancreas. Abdomen; Glycoproteins - blood; Humans; Immunoglobulins - blood; Jaundice, Obstructive - blood; Jaundice, Obstructive - complications; Lectins, C-Type - blood; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Middle Aged; Molecular Diagnostics; Molecular Medicine; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Oncology; Pancreatic cancer; Pancreatic Juice - cytology; Pancreatic Neoplasms - blood; Pancreatic Neoplasms - diagnosis; Pancreatitis-Associated Proteins; Receptors, Polymeric Immunoglobulin - analysis; Tumors; PIGR; pancreatic cancer; ITIH3; complement 5a; biomarker; biliary obstruction; Performance evaluation; Biological marker; Complement; Malignant tumor; Biliary tract disease; Biliary tract obstruction; Cancerology; Pancreas cancer; Digestive diseases; Serum; Performance; Cancer; Pancreatic disease
• ISSN: 0007-0920; 1532-1827; 1532-1827
• DOI: 10.1038/bjc.2013.150

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, α 1- 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.