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Anderson KS , Sibani S , Wallstrom G , Qiu J , Mendoza EA , Raphael J , Hainsworth E , Montor WR , Wong J , Park JG , Lokko N , Logvinenko T , Ramachandran N , Godwin AK , Marks J , Engstrom P , LaBaer J
Protein Microarray Signature of Autoantibody Biomarkers for the Early Detection of Breast Cancer
Journal of Proteome Research. 2011 Jan;10(1) :85-96
PMCID: PMC3158028   
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Abstract
Cancer patients spontaneously generate autoantibodies (AAb) to tumor-derived proteins. To detect AAb, we have probed novel high-density custom protein microarrays (NAPPA) expressing 4988 candidate tumor antigens with sera from patients with early stage breast cancer (IBC), and bound IgG was measured. We used a three-phase serial screening approach. First, a prescreen was performed to eliminate uninformative antigens. Sera from stage I-III IBC (n = 53) and healthy women (n = 53) were screened for AAb to all 4988 protein antigens. Antigens were selected if the 95th percentile of signal of cases and controls were significantly different (p < 0.05) and if the number of cases with signals above the 95th percentile of controls was significant (p < 0.05). These 761 antigens were screened using an independent set of IBC sera (n = 51) and sera from women with benign breast disease (BBD) (n = 39). From these, 119 antigens had a partial area under the ROC curve (p < 0.05), with sensitivities ranging from 9-40% at > 91% specificity. Twenty-eight of these antigens were confirmed using an independent serum cohort (n = 51 cases/38 controls, p < 0.05). Using all 28 AAb, a classifier was identified with a sensitivity of 80.8% and a specificity of 61.6% (AUC = 0.756). These are potential biomarkers for the early detection of breast cancer.
Notes
Anderson, Karen S. Sibani, Sahar Wallstrom, Garrick Qiu, Ji Mendoza, Eliseo A. Raphael, Jacob Hainsworth, Eugenie Montor, Wagner R. Wong, Jessica Park, Jin G. Lokko, Naa Logvinenko, Tanya Ramachandran, Niroshan Godwin, Andrew K. Marks, Jeffrey Engstrom, Paul LaBaer, Joshua Amer chemical soc Washington 701iq