Tumor-associated autoantibodies as early detection markers for ovarian cancer? A prospective evaluation.
File(s)Tumor associated autoantibodies-Kaaks R.pdf (163.23 KB)
Accepted version
Author(s)
Type
Journal Article
Abstract
Immuno-proteomic screening has identified several tumor-associated autoantibodies (AAb) that may have diagnostic capacity for invasive epithelial ovarian cancer, with AAbs to P53 proteins and cancer-testis antigens (CTAGs) as prominent examples. However, the early detection potential of these AAbs has been insufficiently explored in prospective studies. We performed ELISA measurements of AAbs to CTAG1A, CTAG2, P53 and NUDT11 proteins, for 194 patients with ovarian cancer and 705 matched controls from the European EPIC cohort, using serum samples collected up to 36 months prior to diagnosis under usual care. CA125 was measured using electrochemo-luminiscence. Diagnostic discrimination statistics were calculated by strata of lead-time between blood collection and diagnosis. With lead times ≤6 months, ovarian cancer detection sensitivity at 0.98 specificity (SE98) varied from 0.19 [95% CI 0.08-0.40] for CTAG1A, CTAG2 and NUDT1 to 0.23 [0.10-0.44] for P53 (0.33 [0.11-0.68] for high-grade serous tumors). However, at longer lead-times, the ability of these AAb markers to distinguish future ovarian cancer cases from controls declined rapidly; at lead times >1 year, SE98 estimates were close to zero (all invasive cases, range: 0.01-0.11). Compared to CA125 alone, combined logistic regression scores of AAbs and CA125 did not improve detection sensitivity at equal level of specificity. The added value of these selected AAbs as markers for ovarian cancer beyond CA125 for early detection is therefore limited.
Date Issued
2018-02-01
Date Acceptance
2018-02-01
Citation
International Journal of Cancer, 2018, 143 (3), pp.515-526
ISSN
0020-7136
Publisher
Wiley
Start Page
515
End Page
526
Journal / Book Title
International Journal of Cancer
Volume
143
Issue
3
Copyright Statement
© 2018 UICC. This is the accepted version of the following article: Tumor-associated autoantibodies as early detection markers forovarian cancer? A prospective evaluation, Int. J. Cancer: 143, 515–526, which has been published in final form at https://dx.doi.org/10.1002/ijc.31335
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/29473162
Subjects
antibodies
early detection
prospective validation
Publication Status
Published
Coverage Spatial
United States