Comparison of the tumor cell secretome and patient sera for an accurate serum-based diagnosis of pancreatic ductal adenocarcinoma
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Shakhawan Mustafa1,2,*, Longqiang Pan1,*, Aseel Marzoq1, Malak Fawaz1, Laureen Sander1, Felix Rückert3, Andrea Schrenk3, Christina Hartl1, Rico Uhler1, Adem Yildirim1, Oliver Strobel4, Thilo Hackert4, Nathalia Giese4, Markus W. Büchler4, Jörg D. Hoheisel1,*, Mohamed Saiel Saeed Alhamdani1,*
1Division of Functional Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany
2Kurdistan Institution for Strategic Studies and Scientific Research, Kurdistan Region, Iraq
3Chirurgische Klinik, Universitätsmedizin Mannheim, Theodor-Kutzer-Ufer 1-3, Mannheim, Germany
4Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
*These authors have contributed equally to this work
Mohamed Saiel Saeed Alhamdani, email: firstname.lastname@example.org
Keywords: secretome, pancreatic cancer, biomarkers, cell lines, antibody microarray
Received: February 09, 2016 Accepted: December 25, 2016 Published: January 2, 2017
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.
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