title: Mining the malignant ascites proteome for pancreatic cancer biomarkers.
abstract: Pancreatic cancer (PC) is one of the most lethal malignancies and disease-specific biomarkers are desperately needed for better diagnosis, prognosis, monitoring treatment efficacy and for accelerating the development of novel targeted therapeutics. Being an advanced stage manifestation and a proximal fluid in contact with cancer tissues, the ascitic fluid presents itself as a promising rich source of biomarkers. Herein, we present a comprehensive proteomic analysis of pancreatic ascitic fluid. To fractionate the complex ascites proteome, we adopted a multi-dimensional chromatographic approach that included size-exclusion, ion-exchange and lectin-affinity chromatographic techniques. Our detailed proteomic analysis with high-resolution Orbitrap(®)  mass spectrometer resulted in the identification of 816 proteins. We followed rigorous filtering criteria that consisted of PC-specific information obtained from three publicly available databases (Oncomine, Protein Atlas and Unigene) to segregate 20 putative biomarker candidates for future validation. Since these proteins are of membranous and extra-cellular origin, most are glycosylated, and many of them are over-expressed in cancer tissues, the probability of these proteins entering the peripheral blood circulation is high. Their validation as serological PC biomarkers in the future is highly warranted.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
authors.forename: Hari
authors.initials: H
authors.lastname: Kosanam
authors.forename: Shalini
authors.initials: S
authors.lastname: Makawita
authors.forename: Bramford
authors.initials: B
authors.lastname: Judd
authors.forename: Alice
authors.initials: A
authors.lastname: Newman
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Diamandis
mesh_terms: D000368:Aged; D001201:Ascites / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000302:isolation & purification / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D020543:Proteome / Q000032:analysis* / Q000302:isolation & purification / Q000378:metabolism; D040901:Proteomics / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor; D020543:Proteome