Serial analysis of 38 proteins during the progression of human breast tumor in mice using an antibody colocalization microarray.
Bottom Line: The profiles of 38 proteins detected in sera from these animals were analyzed by clustering, and we identified 10 proteins with the greatest relative increase in serum concentration that correlated with growth of the primary mammary tumor.Next, the sensitivity and specificity of individual and optimal protein panels were calculated, showing high accuracy as early as week 2.These results provide a foundation for studies of tumor growth through measuring serial changes of protein concentration in animal models.
Affiliation: From the ‡Biomedical Engineering Department, §McGill University and Genome Quebec Innovation Centre.Show MeSH
Related in: MedlinePlus
Mentions: The sensitivity and specificity were computed for six individual proteins whose AUC = 1 at week 3 using either the absolute or differential method. The optimal protein panel comprising CEA, FAS, uPAR, and IL-8 was computed using an absolute threshold of two standard deviations above the average of the control mice or using the differential method with a limit set as the average standard deviation above the value at weeks −1 and 0 (see “Experimental Procedures” for details). The sensitivity and specificity for each time point are shown in Fig. 7. At week 2, the sensitivities of G-CSF and IL-8 were higher for the differential threshold, and those of uPA, MMP-3, and EGFR were higher for the absolute threshold. The sensitivity improved monotonically for most individual proteins. Relatively large fluctuations are observed for the specificity that can be accounted for by the small number of control mice. CEA gives the most accurate classification with both measurements between weeks 2 and 6 because the assay signals in tumor-bearing mice are higher than those in the control mice. The specificity is similar for both methods except for IL-8 and uPA. EGFR showed a relatively low sensitivity using the differential method that can be ascribed to the fluctuations in concentration observed in our measurements. Despite the fluctuations observed, our measurements achieved relatively high sensitivity and specificity starting from as early as the 2nd week depending on the proteins in question.
Affiliation: From the ‡Biomedical Engineering Department, §McGill University and Genome Quebec Innovation Centre.