title: Confounding effect of obstructive jaundice in the interpretation of proteomic plasma profiling data for pancreatic cancer.
abstract: It is well established that variation in sampling, processing and storage protocols can alter the levels of potential biomarkers in serum and plasma. Here, using pancreatic cancer as an example, we demonstrate that consideration of clinical parameters related to the patient's illness is equally important when seeking cancer-specific biomarkers. Bile duct-obstruction is a feature of pancreatic disease that can cause jaundice. Comparing patients with pancreatic cancer, chronic pancreatitis or biliary duct obstruction, we observed that the plasma levels of apolipoprotein A1, transthyretin, and apolipoprotein E, when examined in isolation, were each associated with pancreatic cancer. However, when the effect of bile duct obstruction was considered, only transthyretin levels were independently associated with cancer likelihood. Our results demonstrate the importance of accounting for disease-related confounding factors when analyzing data for the detection of cancer biomarkers.
authors.affiliation: Division of Surgery and Oncology, Royal Liverpool University Hospital, Liverpool L68 3 GA, UK.
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.forename: Sarah
authors.initials: S
authors.lastname: Tonack
authors.forename: Richard
authors.initials: R
authors.lastname: Smith
authors.forename: Susanna
authors.initials: S
authors.lastname: Dodd
authors.forename: Rosalind E
authors.initials: RE
authors.lastname: Jenkins
authors.forename: Neil
authors.initials: N
authors.lastname: Kitteringham
authors.forename: William
authors.initials: W
authors.lastname: Greenhalf
authors.forename: Paula
authors.initials: P
authors.lastname: Ghaneh
authors.forename: John P
authors.initials: JP
authors.lastname: Neoptolemos
authors.forename: Eithne
authors.initials: E
authors.lastname: Costello
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen / Q000096:biosynthesis; D002779:Cholestasis / Q000097:blood / Q000150:complications / Q000175:diagnosis; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D041781:Jaundice, Obstructive / Q000097:blood* / Q000150:complications / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000150:complications / Q000175:diagnosis*; D040901:Proteomics / Q000379:methods*; D012372:ROC Curve; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen