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Int J Cancer. 2018 Aug 1;143(3):515-526. doi: 10.1002/ijc.31335. Epub 2018 Mar 8.

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

Author information

1
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ) Heidelberg, Germany.
2
Virginia G. Piper Center for Personal Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ.
3
Unit of Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark.
4
Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark.
5
CESP, INSERM U1018, Univ. Paris-Sud, UVSQ, Université Paris-Saclay, Villejuif Cedex, F-94805, France.
6
Gustave Roussy, Villejuif, F-94805, France.
7
International Agency for Research on Cancer, Lyon, France.
8
Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbrücke (DIfE), Nuthetal, Germany.
9
Hellenic Health Foundation, Athens, Greece.
10
WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
11
Department of Clinical Sciences and Community Health Università degli Studi di Milano, Milano, Italy.
12
Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, Milano, 20133, Italy.
13
Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
14
Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for the Study and Prevention of Cancer (ISPO), Florence, Italy.
15
Cancer Registry and Histopathology Unit, "Civic - M.P. Arezzo" Hospital, ASP Ragusa, Italy.
16
Department of Medical Sciences, University of Torino and Human Genetics Foundation - HuGeF, Torino, Italy.
17
Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
18
Faculty of Health Sciences, Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
19
Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway.
20
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
21
Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland.
22
Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs, GRANADA, Hopitales Universitarios de Granada/Universidad de Granada, Granada, Spain.
23
CIBER de Epidemiolgía y Salud Pública (CIBERESP), Spain.
24
Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.
25
Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain.
26
Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
27
Centro de Investigación Biomédica En Red (CIBER), Navarra Public Health Institute, Pamplona, Spain. IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
28
Basque Regional Health Department, Public Health Division and BioDonostia Research Institute and CIBERESP, San Sebastian, Spain.
29
Department of Medical Biosciences, Umeå University, Umeå, 901 85, Sweden.
30
Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden.
31
Department of Surgery, Skane University Hospital, Lund University, Malmö, Sweden.
32
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
33
Faculty of Medicine, School of Public Health, Imperial College London, London, United Kingdom.
34
University of Hawaii Cancer Center, Cancer Epidemiology Program, Honolulu, HI.
35
Brigham and Women's Hospital, Ob/Gyn Epidemiology Center, Boston, MA.
36
Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, MS.

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.

KEYWORDS:

antibodies; early detection; prospective validation

PMID:
29473162
PMCID:
PMC6019150
[Available on 2019-08-01]
DOI:
10.1002/ijc.31335
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