A Quantitative Proteomic Approach of the Different Stages of Colorectal Cancer Establishes OLFM4 as a New Nonmetastatic Tumor Marker

TitreA Quantitative Proteomic Approach of the Different Stages of Colorectal Cancer Establishes OLFM4 as a New Nonmetastatic Tumor Marker
Type de publicationArticle de revue
AuteurBesson, Damien, Pavageau, Aude-Hélène, Valo, Isabelle , Bourreau, Anthony, Bélanger, Audrey, Eymerit-Morin, Caroline, Moulière, Alice, Chassevent, Agnès, Boisdron-Celle, Michèle , Morel, Alain , Solassol, Jerôme, Campone, Mario, Gamelin, Erick, Barré, Benjamin, Coqueret, Olivier , Guette, Catherine
EditeurAmerican Society for Biochemistry and Molecular Biology
TypeArticle scientifique dans une revue à comité de lecture
Année2011
LangueAnglais
Date2011/01/12
Numéro12
Volume10
Titre de la revueMolecular & Cellular Proteomics
ISSN1535-9484
Résumé en anglais

Expression profiles represent new molecular tools that are useful to characterize the successive steps of tumor progression and the prediction of recurrence or chemotherapy response. In this study, we have used quantitative proteomic analysis to compare different stages of colorectal cancer. A combination of laser microdissection, OFFGEL separation, iTRAQ labeling, and MALDI-TOF/TOF MS was used to explore the proteome of 28 colorectal cancer tissues. Two software packages were used for identification and quantification of differentially expressed proteins: Protein Pilot and iQuantitator. Based on ∼1,190,702 MS/MS spectra, a total of 3138 proteins were identified, which represents the largest database of colorectal cancer realized to date and demonstrates the value of our quantitative proteomic approach. In this way, individual protein expression and variation have been identified for each patient and for each colorectal dysplasia and cancer stage (stages I–IV). A total of 555 proteins presenting a significant fold change were quantified in the different stages, and this differential expression correlated with immunohistochemistry results reported in the Human Protein Atlas database. To identify a candidate biomarker of the early stages of colorectal cancer, we focused our study on secreted proteins. In this way, we identified olfactomedin-4, which was overexpressed in adenomas and in early stages of colorectal tumors. This early stage overexpression was confirmed by immunohistochemistry in 126 paraffin-embedded tissues. Our results also indicate that OLFM4 is regulated by the Ras-NF-κB2 pathway, one of the main oncogenic pathways deregulated in colorectal tumors.

URL de la noticehttp://okina.univ-angers.fr/publications/ua9171
DOI10.1074/mcp.M111.009712
Lien vers le document

http://dx.doi.org/10.1074/mcp.M111.009712

Titre abrégéMol Cell Proteomics