Autoantibody Signature for the Serologic Detection of Ovarian Cancer

Sera
from patients with ovarian cancer contain autoantibodies (AAb)
to tumor-derived proteins that are potential biomarkers for early
detection. To detect AAb, we probed high-density programmable protein
microarrays (NAPPA) expressing 5177 candidate tumor antigens with
sera from patients with serous ovarian cancer (n =
34 cases/30 controls) and measured bound IgG. Of these, 741 antigens
were selected and probed with an independent set of ovarian cancer
sera (n = 60 cases/60 controls). Twelve potential
autoantigens were identified with sensitivities ranging from 13 to
22% at >93% specificity. These were retested using a Luminex bead
array using 60 cases and 60 controls, with sensitivities ranging from
0 to 31.7% at 95% specificity. Three AAb (p53, PTPRA, and PTGFR) had
area under the curve (AUC) levels >60% (p <
0.01),
with the partial AUC (SPAUC) over 5 times greater than for a nondiscriminating
test (p < 0.01). Using a panel of the top three
AAb (p53, PTPRA, and PTGFR), if at least two AAb were positive, then
the sensitivity was 23.3% at 98.3% specificity. AAb to at least one
of these top three antigens were also detected in 7/20 sera (35%)
of patients with low CA 125 levels and 0/15 controls. AAb to p53,
PTPRA, and PTGFR are potential biomarkers for the early detection
of ovarian cancer.