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

Rudolf Kaaks, Renée Turzanski Fortner, Anika Hüsing, Myrto Barrdahl, Marika Hopper, Theron Johnson, Anne Tjønneland, Louise Hansen, Kim Overvad, Agnès Fournier, Marie Christine Boutron-Ruault, Marina Kvaskoff, Laure Dossus, Mattias Johansson, Heiner Boeing, Antonia Trichopoulou, Vassiliki Benetou, Carlo La Vecchia, Sabina Sieri, Amalia MattielloDomenico Palli, Rosario Tumino, Giuseppe Matullo, N. Charlotte Onland-Moret, Inger T. Gram, Elisabete Weiderpass, Maria Jose Sánchez, Carmen Navarro Sanchez, Eric J. Duell, Eva Ardanaz, Nerea Larranaga, Eva Lundin, Annika Idahl, Karin Jirström, Björn Nodin, Ruth C. Travis, Elio Riboli, Melissa Merritt, Dagfinn Aune, Kathryn Terry, Daniel W. Cramer, Karen Anderson

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
JournalInternational Journal of Cancer
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Autoantibodies
Ovarian Neoplasms
Neoplasms
Testicular Neoplasms
Proteomics
Proteins
Logistic Models
Enzyme-Linked Immunosorbent Assay
Prospective Studies
Antigens
Serum

Keywords

  • Antibodies
  • Early detection
  • Prospective validation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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; Fournier, Agnès; Boutron-Ruault, Marie Christine; Kvaskoff, Marina; Dossus, Laure; Johansson, Mattias; Boeing, Heiner; Trichopoulou, Antonia; Benetou, Vassiliki; La Vecchia, Carlo; Sieri, Sabina; Mattiello, Amalia; Palli, Domenico; Tumino, Rosario; Matullo, Giuseppe; Onland-Moret, N. Charlotte; Gram, Inger T.; Weiderpass, Elisabete; Sánchez, Maria Jose; Navarro Sanchez, Carmen; Duell, Eric J.; Ardanaz, Eva; Larranaga, Nerea; Lundin, Eva; Idahl, Annika; Jirström, Karin; Nodin, Björn; Travis, Ruth C.; Riboli, Elio; Merritt, Melissa; Aune, Dagfinn; Terry, Kathryn; Cramer, Daniel W.; Anderson, Karen.

In: International Journal of Cancer, 01.01.2018.

Research output: Contribution to journalArticle

Kaaks, R, Fortner, RT, Hüsing, A, Barrdahl, M, Hopper, M, Johnson, T, Tjønneland, A, Hansen, L, Overvad, K, Fournier, A, Boutron-Ruault, MC, Kvaskoff, M, Dossus, L, Johansson, M, Boeing, H, Trichopoulou, A, Benetou, V, La Vecchia, C, Sieri, S, Mattiello, A, Palli, D, Tumino, R, Matullo, G, Onland-Moret, NC, Gram, IT, Weiderpass, E, Sánchez, MJ, Navarro Sanchez, C, Duell, EJ, Ardanaz, E, Larranaga, N, Lundin, E, Idahl, A, Jirström, K, Nodin, B, Travis, RC, Riboli, E, Merritt, M, Aune, D, Terry, K, Cramer, DW & Anderson, K 2018, 'Tumor-associated autoantibodies as early detection markers for ovarian cancer? A prospective evaluation', International Journal of Cancer. https://doi.org/10.1002/ijc.31335
Kaaks, Rudolf ; Fortner, Renée Turzanski ; Hüsing, Anika ; Barrdahl, Myrto ; Hopper, Marika ; Johnson, Theron ; Tjønneland, Anne ; Hansen, Louise ; Overvad, Kim ; Fournier, Agnès ; Boutron-Ruault, Marie Christine ; Kvaskoff, Marina ; Dossus, Laure ; Johansson, Mattias ; Boeing, Heiner ; Trichopoulou, Antonia ; Benetou, Vassiliki ; La Vecchia, Carlo ; Sieri, Sabina ; Mattiello, Amalia ; Palli, Domenico ; Tumino, Rosario ; Matullo, Giuseppe ; Onland-Moret, N. Charlotte ; Gram, Inger T. ; Weiderpass, Elisabete ; Sánchez, Maria Jose ; Navarro Sanchez, Carmen ; Duell, Eric J. ; Ardanaz, Eva ; Larranaga, Nerea ; Lundin, Eva ; Idahl, Annika ; Jirström, Karin ; Nodin, Björn ; Travis, Ruth C. ; Riboli, Elio ; Merritt, Melissa ; Aune, Dagfinn ; Terry, Kathryn ; Cramer, Daniel W. ; Anderson, Karen. / Tumor-associated autoantibodies as early detection markers for ovarian cancer? A prospective evaluation. In: International Journal of Cancer. 2018.
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title = "Tumor-associated autoantibodies as early detection markers for ovarian cancer? A prospective evaluation",
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.",
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AU - Kaaks, Rudolf

AU - Fortner, Renée Turzanski

AU - Hüsing, Anika

AU - Barrdahl, Myrto

AU - Hopper, Marika

AU - Johnson, Theron

AU - Tjønneland, Anne

AU - Hansen, Louise

AU - Overvad, Kim

AU - Fournier, Agnès

AU - Boutron-Ruault, Marie Christine

AU - Kvaskoff, Marina

AU - Dossus, Laure

AU - Johansson, Mattias

AU - Boeing, Heiner

AU - Trichopoulou, Antonia

AU - Benetou, Vassiliki

AU - La Vecchia, Carlo

AU - Sieri, Sabina

AU - Mattiello, Amalia

AU - Palli, Domenico

AU - Tumino, Rosario

AU - Matullo, Giuseppe

AU - Onland-Moret, N. Charlotte

AU - Gram, Inger T.

AU - Weiderpass, Elisabete

AU - Sánchez, Maria Jose

AU - Navarro Sanchez, Carmen

AU - Duell, Eric J.

AU - Ardanaz, Eva

AU - Larranaga, Nerea

AU - Lundin, Eva

AU - Idahl, Annika

AU - Jirström, Karin

AU - Nodin, Björn

AU - Travis, Ruth C.

AU - Riboli, Elio

AU - Merritt, Melissa

AU - Aune, Dagfinn

AU - Terry, Kathryn

AU - Cramer, Daniel W.

AU - Anderson, Karen

PY - 2018/1/1

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AB - 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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