Identification of pro-MMP-7 as a serum marker for renal cell carcinoma by use of proteomic analysis.
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 microg/L; range 3.12-30.5 microg/L) compared with healthy controls (median 2.13 microg/L; range 0.17-3.5 microg/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.


CONCLUSIONS
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.
Sarkissian
Gaiane
G
Research and Development Department, Cezanne SAS, Parc Scientifique Georges Besse, Nimes, France. gsarkissian@cezanne.fr
Fergelot
Patricia
P
Lamy
Pierre-Jean
PJ
Patard
Jean-Jacques
JJ
Culine
Stephane
S
Jouin
Patrick
P
Rioux-Leclercq
Nathalie
N
Darbouret
Bruno
B
D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D014408:Biomarkers, Tumor / Q000097:blood* / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000556:secondary; D045744:Cell Line, Tumor; D005260:Female; D015200:Fluoroimmunoassay; D006801:Humans; D007527:Isoenzymes / Q000097:blood / Q000276:immunology; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000097:blood* / Q000276:immunology; D011498:Protein Precursors / Q000097:blood / Q000276:immunology; D012189:Retrospective Studies; D044967:Serum
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D007527:Isoenzymes; D011498:Protein Precursors; D020783:Matrix Metalloproteinase 7