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 Mattiello & 22 others Domenico 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

    2 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

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    KW - Prospective validation

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