title: Comparison of the tumor cell secretome and patient sera for an accurate serum-based diagnosis of pancreatic ductal adenocarcinoma.
abstract: Pancreatic cancer is the currently most lethal malignancy. Toward an accurate diagnosis of the disease in body liquids, we studied the protein composition of the secretomes of 16 primary and established cell lines of pancreatic ductal adenocarcinoma (PDAC). Compared to the secretome of non-tumorous cells, 112 proteins exhibited significantly different abundances. Functionally, the proteins were associated with PDAC features, such as decreased apoptosis, better cell survival and immune cell regulation. The result was compared to profiles obtained from 164 serum samples from two independent cohorts - a training and a test set - of patients with PDAC or chronic pancreatitis and healthy donors. Eight of the 112 secretome proteins exhibited similar variations in their abundance in the serum profile specific for PDAC patients, which was composed of altogether 189 proteins. The 8 markers shared by secretome and serum yielded a 95.1% accuracy of distinguishing PDAC from healthy in a Receiver Operating Characteristic curve analysis, while any number of serum-only markers produced substantially less accurate results. Utility of the identified markers was confirmed by classical enzyme linked immunosorbent assays (ELISAs). The study highlights the value of cell secretome analysis as a means of defining reliable serum biomarkers.
authors.affiliation: Division of Functional Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.|Kurdistan Institution for Strategic Studies and Scientific Research, Kurdistan Region, Iraq.
authors.forename: Shakhawan
authors.initials: S
authors.lastname: Mustafa
authors.affiliation: Division of Functional Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors.forename: Longqiang
authors.initials: L
authors.lastname: Pan
authors.affiliation: Division of Functional Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors.forename: Aseel
authors.initials: A
authors.lastname: Marzoq
authors.affiliation: Division of Functional Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors.forename: Malak
authors.initials: M
authors.lastname: Fawaz
authors.affiliation: Division of Functional Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors.forename: Laureen
authors.initials: L
authors.lastname: Sander
authors.affiliation: Chirurgische Klinik, Universitätsmedizin Mannheim, Theodor-Kutzer-Ufer 1-3, Mannheim, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Rückert
authors.affiliation: Chirurgische Klinik, Universitätsmedizin Mannheim, Theodor-Kutzer-Ufer 1-3, Mannheim, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Schrenk
authors.affiliation: Division of Functional Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Hartl
authors.affiliation: Division of Functional Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors.forename: Rico
authors.initials: R
authors.lastname: Uhler
authors.affiliation: Division of Functional Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors.forename: Adem
authors.initials: A
authors.lastname: Yildirim
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Strobel
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Thilo
authors.initials: T
authors.lastname: Hackert
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Nathalia
authors.initials: N
authors.lastname: Giese
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
authors.affiliation: Division of Functional Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors.forename: Jörg D
authors.initials: JD
authors.lastname: Hoheisel
authors.affiliation: Division of Functional Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors.forename: Mohamed Saiel Saeed
authors.initials: MS
authors.lastname: Alhamdani
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor
keywords: antibody microarray; biomarkers; cell lines; pancreatic cancer; secretome