title: A proteomics approach to identify changes in protein profiles in serum of Familial Adenomatous Polyposis patients.
abstract: Familial adenomatous polyposis (FAP) is one of the most important clinical hereditary forms of inherited susceptibility to colorectal cancer and is characterized by a high degree of phenotypic heterogeneity. We used a mass spectrometry driven-proteomic strategy to identify serum molecules differently expressed in FAP patients. The data obtained were subsequently processed by bioinformatic analysis and confirmed by Western blotting. Significant differences were highlighted in the expression of serum proteins of FAP patients. In particular, two proteins (alpha-2-HS-glycoprotein and apoliprotein D) were down-regulated (about 0.5- and 0.7-fold, respectively) in carpeting versus diffuse FAP patients and healthy donors, while alpha-2-antiplasmin was up-regulated (about 1.4-fold). Moreover, mass spectrometry approach enabled us to identify serum biomarkers specific for two distinct clinical form of FAP, i.e. carpeting and diffuse FAP. In particular, vitronectin was up-regulated (more than 1.4-fold) in diffuse FAP patients versus carpeting FAP and versus healthy donors, and two additional proteins (Haptoglobin and alpha-1-acid glycoprotein 1) were up-regulated in 2 out of 3 carpeting FAP patients. Our study suggests that mass spectrometry combined to a strong bioinformatics analysis is a valuable tool for the identification of quali/quantitative differences in the serum proteome of otherwise indistinguishable FAP phenotypes. Moreover, the definition of a proteomic profile, supported by the supervised classification, is a powerful and highly sensitive approach for the identification molecular signatures that are able to outperform the traditional disease markers and can therefore be efficiently applied for the diagnosis and clinical management of FAP patients.
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica G. Salvatore, Università degli Studi di Catanzaro Magna Graecia, Viale Europa, Campus Universitario Salvatore Venuta, 88100 Catanzaro, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Quaresima
authors.forename: Telma
authors.initials: T
authors.lastname: Crugliano
authors.forename: Marco
authors.initials: M
authors.lastname: Gaspari
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Faniello
authors.forename: Paola
authors.initials: P
authors.lastname: Cosimo
authors.forename: Rosa
authors.initials: R
authors.lastname: Valanzano
authors.forename: Maurizio
authors.initials: M
authors.lastname: Genuardi
authors.forename: Mario
authors.initials: M
authors.lastname: Cannataro
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Veltri
authors.forename: Francesco
authors.initials: F
authors.lastname: Baudi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Doldo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cuda
authors.forename: Salvatore
authors.initials: S
authors.lastname: Venuta
authors.forename: Francesco
authors.initials: F
authors.lastname: Costanzo
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000097:blood / Q000235:genetics*; D053399:Apolipoproteins D / Q000097:blood / Q000235:genetics*; D001798:Blood Proteins / Q000235:genetics*; D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics*; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D006242:Haptoglobins / Q000235:genetics; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D013058:Mass Spectrometry; D020543:Proteome; D040901:Proteomics / Q000379:methods; D012016:Reference Values; D012709:Serum Albumin / Q000235:genetics; D060749:alpha-2-HS-Glycoprotein
chemical_list: C556354:AHSG protein, human; D053399:Apolipoproteins D; D001798:Blood Proteins; D006242:Haptoglobins; D007074:Immunoglobulin G; D020543:Proteome; D012709:Serum Albumin; D060749:alpha-2-HS-Glycoprotein; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase