Reference : Novel comprehensive approach for accessible biomarker identification and absolute qua...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/99387
Novel comprehensive approach for accessible biomarker identification and absolute quantification from precious human tissues
English
Turtoi, Andrei mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases >]
Dumont, Bruno mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases > >]
Greffe, Yannick [Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases > >]
Blomme, Arnaud [Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases >]
Mazzucchelli, Gabriel mailto [Université de Liège - ULg > > Center for Analytical Research and Technology (CART) >]
Delvenne, Philippe mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques >]
MUTIJIMA NZARAMBA, Eugène mailto [Centre Hospitalier Universitaire de Liège - CHU > > Anatomie pathologique >]
LIFRANGE, Eric mailto [Centre Hospitalier Universitaire de Liège - CHU > > Sénologie >]
De Pauw, Edwin mailto [Université de Liège - ULg > Département de chimie (sciences) > GIGA-R : Laboratoire de spectrométrie de masse (L.S.M.) >]
Castronovo, Vincenzo mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire >]
1-Jul-2011
Journal of Proteome Research
American Chemical Society
10
7
3160-82
Yes (verified by ORBi)
International
1535-3893
1535-3907
Washington
DC
[en] proteomics ; accessible proteins ; cancer biomarkers ; glycoproteins,
[en] The identification of specific biomarkers obtained directly from human pathological lesions remains a major challenge, because the amount of tissue available is often very limited. We have developed a novel, comprehensive, and efficient method permitting the identification and absolute quantification of potentially accessible proteins in such precious samples. This protein subclass comprises cell membrane associated and extracellular proteins, which are reachable by systemically deliverable substances and hence especially suitable for diagnosis and targeted therapy applications. To isolate such proteins, we exploited the ability of chemically modified biotin to label ex vivo accessible proteins and the fact that most of these proteins are glycosylated. This approach consists of three successive steps involving first the linkage of potentially accessible proteins to biotin molecules followed by their purification. The remaining proteins are then subjected to glycopeptide isolation. Finally, the analysis of the nonglycosylated peptides and their involvement in an in silico method increased the confident identification of glycoproteins. The value of the technique was demonstrated on human breast cancer tissue samples originating from 5 individuals. Altogether, the method delivered quantitative data on more than 400 potentially accessible proteins (per sample and replicate). In comparison to biotinylation or glycoprotein analysis alone, the sequential method significantly increased the number (≥30% and ≥50% respectively) of potentially therapeutically and diagnostically valuable proteins. The sequential method led to the identification of 93 differentially modulated proteins, among which several were not reported to be associated with the breast cancer. One of these novel potential biomarkers was CD276, a cell membrane-associated glycoprotein. The immunohistochemistry analysis showed that CD276 is significantly differentially expressed in a series of breast cancer lesions. Due to the fact that our technology is applicable to any type of tissue biopsy, it bears the ability to accelerate the discovery of new relevant biomarkers in a broad spectrum of pathologies.
Giga-Cancer
University of Liege ARC IDEA, FNRS, EU FP7 ADAMANT
http://hdl.handle.net/2268/99387
10.1021/pr200212r
FP7 ; 201342 - ADAMANT - ANTIBODY DERIVATIVES AS MOLECULAR AGENTS FOR NEOPLASTIC TARGETING

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