title: A quantitative proteomic approach of the different stages of colorectal cancer establishes OLFM4 as a new nonmetastatic tumor marker.
abstract: 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.
authors: Institut de Cancérologie de l'Ouest, Paul Papin Cancer Center, INSERM U892, Angers, France.
authors: Damien
authors: D
authors: Besson
authors: Aude-Hélène
authors: AH
authors: Pavageau
authors: Isabelle
authors: I
authors: Valo
authors: Anthony
authors: A
authors: Bourreau
authors: Audrey
authors: A
authors: Bélanger
authors: Caroline
authors: C
authors: Eymerit-Morin
authors: Alice
authors: A
authors: Moulière
authors: Agnès
authors: A
authors: Chassevent
authors: Michelle
authors: M
authors: Boisdron-Celle
authors: Alain
authors: A
authors: Morel
authors: Jerôme
authors: J
authors: Solassol
authors: Mario
authors: M
authors: Campone
authors: Erick
authors: E
authors: Gamelin
authors: Benjamin
authors: B
authors: Barré
authors: Olivier
authors: O
authors: Coqueret
authors: Catherine
authors: C
authors: Guette
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000236:Adenoma / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006031:Glycosylation; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D061346:Laser Capture Microdissection; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020543:Proteome / Q000378:metabolism; D040901:Proteomics; D015203:Reproducibility of Results; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C454127:OLFM4 protein, human; D020543:Proteome; D016179:Granulocyte Colony-Stimulating Factor; D018631:ras Proteins