HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: clinchem.2007.090837v1 54/3/574    most recent Submit an electronic Letter to the Editor about this paper Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sarkissian, G. Articles by Darbouret, B. Search for Related Content PubMed PubMed Citation Articles by Sarkissian, G. Articles by Darbouret, B. Related Collections Proteomics and Protein Markers

Identification of Pro-MMP-7 as a Serum Marker for Renal Cell Carcinoma by Use of Proteomic Analysis

¹ Research and Development Department, Cezanne SAS, Parc Scientifique Georges Besse, Nimes, France;² Department of Biochemistry and Molecular Genetics, University Hospital Center-Pontchaillou Hospital, Rennes, France;³ Department of Clinical Laboratory, Val d’Aurelle-Paul Lamarque Cancer Institute, Montpellier, France;⁴ CNRS UMR6061 Genetics and Development, IFR 140, University of Rennes 1, Rennes, France;⁵ IGF, CNRS UMR5203, INSERM, U661, University of Montpellier 1, University of Montpellier 2, Montpellier, France.

^aAddress correspondence to this author at: Research and Development Department, Cezanne SAS, Parc Scientifique Georges Besse, 280 Allée Graham Bell, 30035 Nimes Cedex 1, France. Fax 33-4-66-36-52-03; e-mail gsarkissian{at}cezanne.fr.

Background: No validated renal cell carcinoma (RCC) marker is known for detection of asymptomatic disease in selected populations or for prognostic purposes or treatment monitoring. We identified immunogenic proteins as tumor markers for RCC by combining conventional proteome analysis with serological screening, and we investigated the diagnostic clinical value of such markers in serum.

Methods: We studied the immunogenic protein expression profile of CAL 54, a human RCC cell line, by 2-dimensional electrophoresis combined with immunoblotting using sera from healthy donors compared with RCC patients. We developed a homogeneous, fluorescent, dual-monoclonal immunoassay for metalloproteinase 7 (MMP-7) and used it to measure MMP-7 in sera from 30 healthy donors, 30 RCC patients, and 40 control patients.

Results: Pro-MMP-7 (29 kDa; pI 7.7) in the CAL 54 cell line secretome was an immunogenic protein reactive with RCC patient sera but not with control sera. The concentrations of pro-MMP-7 were increased (P <0.0001) in sera of RCC patients (median 7.56 µg/L; range 3.12–30.5 µg/L) compared with healthy controls (median 2.13 µg/L; range 0.17–3.5 µg/L). Serum pro-MMP-7 had a sensitivity of 93% (95% CI 78%–99%) at a specificity of 75% (59%–87%) for RCC in the samples tested.

Conclusion: Proteomics technology combined with serology led to the identification of serum pro-MMP-7 as a marker of RCC and represents a powerful tool in searching for candidate proteins as biomarkers.