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: A hierarchical clustering was performed for 38 human proteins based on the average concentration across the 11 mice at each time point (Fig. 2). Ten proteins, clustered from EGFR down to MMP-3, show increasing concentrations over time. The next cluster of seven proteins from NT-3 to TNF-RII also shows a clear increase of average values over time but with significant fluctuation. Further down in the list, no clear trends are visible. The proteins clustered at the bottom, starting from IL-4, show moderate signals at week −1 and low signal levels for time point 6, and some of them are relatively high for time point 5. HER2 was not detected in the mouse serum as expected because triple-negative breast cancer cells were used to grow tumors. CA 15-3, which is used clinically to evaluate response to therapy in breast cancer (28), did not cluster with the discriminating proteins at the top. CA15-3 did, however, increase in concentration during the first 3 weeks after cancer cell injection but then decreased, and fluctuations were observed in individual mice. For further analysis, we decided to focus on the 10 proteins clustered at the top of the heat map.
Affiliation: From the ‡Biomedical Engineering Department, §McGill University and Genome Quebec Innovation Centre.