title: Serial analysis of 38 proteins during the progression of human breast tumor in mice using an antibody colocalization microarray.
abstract: Proteins in serum or plasma hold great potential for use in disease diagnosis and monitoring. However, the correlation between tumor burden and protein biomarker concentration has not been established. Here, using an antibody colocalization microarray, the protein concentration in serum was measured and compared with the size of mammary xenograft tumors in 11 individual mice from the time of injection; seven blood samples were collected from each tumor-bearing mouse as well as control mice on a weekly basis. 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. To evaluate the diagnosis of cancer based on these proteins using either an absolute threshold (i.e. a concentration cutoff) or self-referenced differential threshold based on the increase in concentration before cell injection, receiver operating characteristic curves were produced for 10 proteins with increased concentration, and the area under curve was calculated for each time point based on a single protein or on a panel of proteins, in each case showing a rapid increase of the area under curve. 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.
authors: From the ‡Biomedical Engineering Department, §McGill University and Genome Quebec Innovation Centre.
authors: Huiyan
authors: H
authors: Li
authors: From the ‡Biomedical Engineering Department, §McGill University and Genome Quebec Innovation Centre.
authors: Sébastien
authors: S
authors: Bergeron
authors: ‖Rosalind and Morris Goodman Cancer Research Centre, and.
authors: Matthew G
authors: MG
authors: Annis
authors: ‖Rosalind and Morris Goodman Cancer Research Centre, and.
authors: Peter M
authors: PM
authors: Siegel
authors: From the ‡Biomedical Engineering Department, §McGill University and Genome Quebec Innovation Centre, **Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec H3A 0G1, Canada david.juncker@mcgill.ca.
authors: David
authors: D
authors: Juncker
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016000:Cluster Analysis; D018450:Disease Progression; D005260:Female; D006801:Humans; D007118:Immunoassay; D015674:Mammary Neoplasms, Animal / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism*; D040081:Protein Array Analysis / Q000379:methods*; D012372:ROC Curve; D015203:Reproducibility of Results; D013997:Time Factors; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D000912:Antibodies, Neoplasm; D014408:Biomarkers, Tumor; D001798:Blood Proteins; D009363:Neoplasm Proteins