A proteomics approach to identify changes in protein profiles in serum of Familial Adenomatous Polyposis patients.
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.
Quaresima
Barbara
B
Dipartimento di Medicina Sperimentale e Clinica G. Salvatore, Università degli Studi di Catanzaro Magna Graecia, Viale Europa, Campus Universitario Salvatore Venuta, 88100 Catanzaro, Italy.
Crugliano
Telma
T
Gaspari
Marco
M
Faniello
Maria Concetta
MC
Cosimo
Paola
P
Valanzano
Rosa
R
Genuardi
Maurizio
M
Cannataro
Mario
M
Veltri
Pierangelo
P
Baudi
Francesco
F
Doldo
Patrizia
P
Cuda
Giovanni
G
Venuta
Salvatore
S
Costanzo
Francesco
F
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
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