Protein microarray signature of autoantibody biomarkers for the early detection of breast cancer.
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.
Cancer Vaccine Center, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. kanderson@partners.org
Karen S
KS
Anderson
Sahar
S
Sibani
Garrick
G
Wallstrom
Ji
J
Qiu
Eliseo A
EA
Mendoza
Jacob
J
Raphael
Eugenie
E
Hainsworth
Wagner R
WR
Montor
Jessica
J
Wong
Jin G
JG
Park
Naa
N
Lokko
Tanya
T
Logvinenko
Niroshan
N
Ramachandran
Andrew K
AK
Godwin
Jeffrey
J
Marks
Paul
P
Engstrom
Joshua
J
Labaer
D000951:Antigens, Neoplasm / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000097:blood* / Q000378:metabolism; D001943:Breast Neoplasms / Q000097:blood / Q000175:diagnosis*; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D040081:Protein Array Analysis / Q000379:methods*; D040901:Proteomics / Q000379:methods*; D012372:ROC Curve; D012044:Regression Analysis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D025262:Vacuolar Proton-Translocating ATPases / Q000097:blood / Q000235:genetics / Q000378:metabolism
C089598:ATP6AP1 protein, human; D000951:Antigens, Neoplasm; D001323:Autoantibodies; D015415:Biomarkers; D025262:Vacuolar Proton-Translocating ATPases