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Tumor-associated autoantibodies as early detection markers for ovarian cancer? A prospective evaluation

Kaaks, Rudolf; Fortner, Renée Turzanski; Hüsing, Anika; Barrdahl, Myrto; Hopper, Marika; Johnson, Theron; Tjønneland, Anne; Hansen, Louise; Overvad, Kim and Fournier, Agnès, et al. (2018) In International Journal of Cancer 143(3). p.515-526
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... (More)

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.

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publication status
published
subject
keywords
Antibodies, Early detection, Prospective validation
in
International Journal of Cancer
volume
143
issue
3
pages
515 - 526
publisher
John Wiley & Sons
external identifiers
  • scopus:85043348365
ISSN
0020-7136
DOI
10.1002/ijc.31335
language
English
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yes
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1a14e39c-38f1-4587-a4fa-bbecdb8ef2d1
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2018-03-23 12:13:04
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2019-03-19 03:51:39
@article{1a14e39c-38f1-4587-a4fa-bbecdb8ef2d1,
  abstract     = {<p>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 &gt;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.</p>},
  author       = {Kaaks, Rudolf and Fortner, Renée Turzanski and Hüsing, Anika and Barrdahl, Myrto and Hopper, Marika and Johnson, Theron and Tjønneland, Anne and Hansen, Louise and Overvad, Kim and Fournier, Agnès and Boutron-Ruault, Marie Christine and Kvaskoff, Marina and Dossus, Laure and Johansson, Mattias and Boeing, Heiner and Trichopoulou, Antonia and Benetou, Vassiliki and La Vecchia, Carlo and Sieri, Sabina and Mattiello, Amalia and Palli, Domenico and Tumino, Rosario and Matullo, Giuseppe and Onland-Moret, N. Charlotte and Gram, Inger T. and Weiderpass, Elisabete and Sánchez, Maria Jose and Navarro Sanchez, Carmen and Duell, Eric J. and Ardanaz, Eva and Larranaga, Nerea and Lundin, Eva and Idahl, Annika and Jirström, Karin and Nodin, Björn and Travis, Ruth C. and Riboli, Elio and Merritt, Melissa and Aune, Dagfinn and Terry, Kathryn and Cramer, Daniel W. and Anderson, Karen S.},
  issn         = {0020-7136},
  keyword      = {Antibodies,Early detection,Prospective validation},
  language     = {eng},
  month        = {03},
  number       = {3},
  pages        = {515--526},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {Tumor-associated autoantibodies as early detection markers for ovarian cancer? A prospective evaluation},
  url          = {http://dx.doi.org/10.1002/ijc.31335},
  volume       = {143},
  year         = {2018},
}