Protein microarray signature of autoantibody biomarkers for the early detection of breast cancer.

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.

• Authors: Karen S Anderson, Sahar Sibani, Garrick Wallstrom, Ji Qiu, Eliseo A Mendoza, Jacob Raphael, Eugenie Hainsworth, Wagner R Montor, Jessica Wong, Jin G Park, Naa Lokko, Tanya Logvinenko, Niroshan Ramachandran, Andrew K Godwin, Jeffrey Marks, Paul Engstrom, Joshua Labaer
• Journal: Journal of proteome research (J Proteome Res) Vol. 10 Issue 1 Pg. 85-96 (Jan 07 2011) ISSN: 1535-3907 [Electronic] United States
• PMID: 20977275 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• ATP6AP1 protein, human
• Antigens, Neoplasm
• Autoantibodies
• Biomarkers
• Vacuolar Proton-Translocating ATPases

Topics

• Antigens, Neoplasm (metabolism)
• Autoantibodies (blood, genetics, metabolism)
• Biomarkers (blood, metabolism)
• Breast Neoplasms (blood, diagnosis)
• Case-Control Studies
• Female
• Gene Expression Profiling
• Humans
• Oligonucleotide Array Sequence Analysis (methods)
• Protein Array Analysis (methods)
• Proteomics (methods)
• ROC Curve
• Regression Analysis
• Reproducibility of Results
• Sensitivity and Specificity
• Vacuolar Proton-Translocating ATPases (blood, genetics, metabolism)