Comparison of the tumor cell secretome and patient sera for an accurate serum-based diagnosis of pancreatic ductal adenocarcinoma

// Shakhawan Mustafa 1, 2, * , Longqiang Pan 1, * , Aseel Marzoq 1 , Malak Fawaz 1 , Laureen Sander 1 , Felix Rückert 3 , Andrea Schrenk 3 , Christina Hartl 1 , Rico Uhler 1 , Adem Yildirim 1 , Oliver Strobel 4 , Thilo Hackert 4 , Nathalia Giese 4 , Markus W. Büchler 4 , Jörg D. Hoheisel 1, * , Mohamed Saiel Saeed Alhamdani 1, * 1 Division of Functional Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany 2 Kurdistan Institution for Strategic Studies and Scientific Research, Kurdistan Region, Iraq 3 Chirurgische Klinik, Universitätsmedizin Mannheim, Theodor-Kutzer-Ufer 1-3, Mannheim, Germany 4 Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany * These authors have contributed equally to this work Correspondence to: Mohamed Saiel Saeed Alhamdani, email: m.alhamdani@dkfz.de Keywords: secretome, pancreatic cancer, biomarkers, cell lines, antibody microarray Received: February 09, 2016      Accepted: December 25, 2016      Published: January 2, 2017 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.