title: Identification of novel accessible proteins bearing diagnostic and therapeutic potential in human pancreatic ductal adenocarcinoma.
abstract: Pancreas ductal adenocarcinoma (PDAC) remains a deadly malignancy with poor early diagnostic and no effective therapy. Although several proteomic studies have performed comparative analysis between normal and malignant tissues, there is a lack of clear characterization of proteins that could be of clinical value. Systemically reachable ("potentially accessible") proteins, suitable for imaging technologies and targeted therapies represent a major group of interest. The current study explores potentially accessible proteins overexpressed in PDAC, employing innovative proteomics technologies. In the discovery phase, potentially accessible proteins from fresh human normal and PDAC tissues were ex vivo biotinylated, isolated and identified using 2D-nano-HPLC-MS/MS method. The analysis revealed 422 up-regulated proteins in the tumor, of which 83 (including protein isoforms) were evaluated as potentially accessible. Eleven selected candidates were further confirmed as up-regulated using Western blot and multiple reaction monitoring protein quantification. Of these, transforming growth factor beta-induced (TGFBI), latent transforming growth factor beta binding 2 (LTBP2), and asporin (ASPN) were further investigated by employing large scale immunohistochemistry-based validations. They were found to be significantly expressed in a large group of clinical PDAC samples compared to corresponding normal and inflammatory tissues. In conclusion, TGFBI, LTBP2, and ASPN are novel, overexpressed, and potentially accessible proteins in human PDAC. They bear the potential to be of clinical value for diagnostic and therapeutic applications and merit further studies using in vivo models.
authors.affiliation: Metastasis Research Laboratory, GIGA-Cancer, University Hospital CHU, University of Liege, Bat B23, 4000 Liege, Belgium.
authors.forename: Andrei
authors.initials: A
authors.lastname: Turtoi
authors.forename: Davide
authors.initials: D
authors.lastname: Musmeci
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Wang
authors.forename: Bruno
authors.initials: B
authors.lastname: Dumont
authors.forename: Joan
authors.initials: J
authors.lastname: Somja
authors.forename: Generoso
authors.initials: G
authors.lastname: Bevilacqua
authors.forename: Edwin
authors.initials: E
authors.lastname: De Pauw
authors.forename: Philippe
authors.initials: P
authors.lastname: Delvenne
authors.forename: Vincent
authors.initials: V
authors.lastname: Castronovo
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000737:chemistry; D019921:Biotinylation; D015153:Blotting, Western; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D016000:Cluster Analysis; D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins / Q000032:analysis* / Q000737:chemistry; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins