title: Pancreatic preneoplastic lesions plasma signatures and biomarkers based on proteome profiling of mouse models.
abstract: BACKGROUND
  Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with a mortality that is almost identical to incidence. Because early detected PDAC is potentially curable, blood-based biomarkers that could detect currently developing neoplasia would improve patient survival and management. PDAC develops from pancreatic intraepithelial neoplasia (PanIN) lesions, graded from low grade (PanIN1) to high grade (PanIN3). We made the hypothesis that specific proteomic signatures from each precancerous stage exist and are detectable in plasma.
  
  
  METHODS
  We explored the peptide profiles of microdissected PanIN cells and of plasma samples corresponding to the different PanIN grade from genetically engineered mouse models of PDAC using capillary electrophoresis coupled to mass spectrometry (CE-MS) and Chip-MS/MS.
  
  
  RESULTS
  We successfully characterised differential peptides profiles from PanIN microdissected cells. We found that plasma from tumor-bearing mice and age-matched controls exhibit discriminative peptide signatures. We also determined plasma peptide signatures corresponding to low- and high-grade precancerous step present in the mice pancreas using the two mass spectrometry technologies. Importantly, we identified biomarkers specific of PanIN3.
  
  
  CONCLUSIONS
  We demonstrate that benign and advanced PanIN lesions display distinct plasma peptide patterns. This strongly supports the perspectives of developing a non-invasive screening test for prediction and early detection of PDAC.
authors.affiliation: Proteomics Group, Centre de Recherches en Cancérologie de Toulouse (CRCT), INSERM UMR1037, Université Toulouse III-Paul Sabatier, Toulouse 31037, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Ligat
authors.affiliation: Proteomics Group, Centre de Recherches en Cancérologie de Toulouse (CRCT), INSERM UMR1037, Université Toulouse III-Paul Sabatier, Toulouse 31037, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Saint-Laurent
authors.affiliation: Proteomics Group, Centre de Recherches en Cancérologie de Toulouse (CRCT), INSERM UMR1037, Université Toulouse III-Paul Sabatier, Toulouse 31037, France.
authors.forename: Aïcha
authors.initials: A
authors.lastname: El-Mrani
authors.affiliation: EA 4552, Université Toulouse III-Paul Sabatier, Toulouse 31432, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Gigoux
authors.affiliation: INSERM-US006 ANEXPLO/CREFRE-Histology facility, Toulouse 31024, France.
authors.forename: Talal
authors.initials: T
authors.lastname: Al Saati
authors.affiliation: Centre de Recherches en Cancérologie de Marseille (CRCM), Inserm U1068, Institut Paoli-Calmettes, Université Aix-Marseille, CNRS, UMR7258, Marseille 13288, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Tomasini
authors.affiliation: Centre de Recherches en Cancérologie de Marseille (CRCM), Inserm U1068, Institut Paoli-Calmettes, Université Aix-Marseille, CNRS, UMR7258, Marseille 13288, France.
authors.forename: Jérémy
authors.initials: J
authors.lastname: Nigri
authors.affiliation: Institut de Mathématiques de Toulouse, UMR 5219 CNRS, Université Toulouse III-Paul Sabatier, Toulouse 31062, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Dejean
authors.affiliation: Proteomics Group, Centre de Recherches en Cancérologie de Toulouse (CRCT), INSERM UMR1037, Université Toulouse III-Paul Sabatier, Toulouse 31037, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Pont
authors.affiliation: Centre de Recherches en Cancérologie de Toulouse (CRCT), INSERM UMR1037, Université Toulouse III-Paul Sabatier, Equipe Labellisée Ligue Contre le Cancer, Toulouse 31037, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Baer
authors.affiliation: Centre de Recherches en Cancérologie de Toulouse (CRCT), INSERM UMR1037, Université Toulouse III-Paul Sabatier, Equipe Labellisée Ligue Contre le Cancer, Toulouse 31037, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Guillermet-Guibert
authors.affiliation: Centre de Recherches en Cancérologie de Toulouse (CRCT), INSERM UMR1037, Université Toulouse III-Paul Sabatier, Toulouse 31037, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Cordelier
authors.affiliation: Proteomics Group, Centre de Recherches en Cancérologie de Toulouse (CRCT), INSERM UMR1037, Université Toulouse III-Paul Sabatier, Toulouse 31037, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lopez
authors.affiliation: Centre de Recherches en Cancérologie de Toulouse (CRCT), INSERM UMR1037, Université Toulouse III-Paul Sabatier, Toulouse 31037, France.
authors.forename: Marlène
authors.initials: M
authors.lastname: Dufresne
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood*; D002278:Carcinoma in Situ / Q000097:blood* / Q000737:chemistry / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood* / Q000737:chemistry; D004195:Disease Models, Animal; D051379:Mice; D009363:Neoplasm Proteins / Q000032:analysis / Q000097:blood*; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000737:chemistry; D010455:Peptides / Q000032:analysis / Q000097:blood*; D011230:Precancerous Conditions / Q000097:blood* / Q000737:chemistry / Q000473:pathology; D040081:Protein Array Analysis; D020543:Proteome / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D010455:Peptides; D020543:Proteome