Prospective evaluation of 92 serum protein biomarkers for early detection of ovarian cancer

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Trasias Mukama
  • Renée Turzanski Fortner
  • Verena Katzke
  • Lucas Cory Hynes
  • Agnese Petrera
  • Stefanie M Hauck
  • Theron Johnson
  • Matthias Schulze
  • Catarina Schiborn
  • Kim Overvad
  • María José Sánchez Pérez
  • Marta Crous-Bou
  • María-Dolores Chirlaque
  • Pilar Amiano
  • Eva Ardanaz
  • Eleanor L Watts
  • Ruth C Travis
  • Carlotta Sacerdote
  • Sara Grioni
  • Giovanna Masala
  • Simona Signoriello
  • Rosario Tumino
  • Inger T Gram
  • Torkjel M Sandanger
  • Hanna Sartor
  • Eva Lundin
  • Annika Idahl
  • Alicia K Heath
  • Laure Dossus
  • Elisabete Weiderpass
  • Rudolf Kaaks

Background: CA125 is the best available yet insufficiently sensitive biomarker for early detection of ovarian cancer. There is a need to identify novel biomarkers, which individually or in combination with CA125 can achieve adequate sensitivity and specificity for the detection of earlier-stage ovarian cancer. 

Methods: In the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we measured serum levels of 92 preselected proteins for 91 women who had blood sampled ≤18 months prior to ovarian cancer diagnosis, and 182 matched controls. We evaluated the discriminatory performance of the proteins as potential early diagnostic biomarkers of ovarian cancer. 

Results: Nine of the 92 markers; CA125, HE4, FOLR1, KLK11, WISP1, MDK, CXCL13, MSLN and ADAM8 showed an area under the ROC curve (AUC) of ≥0.70 for discriminating between women diagnosed with ovarian cancer and women who remained cancer-free. All, except ADAM8, had shown at least equal discrimination in previous case-control comparisons. The discrimination of the biomarkers, however, was low for the lag-time of >9–18 months and paired combinations of CA125 with any of the 8 markers did not improve discrimination compared to CA125 alone. 

Conclusion: Using pre-diagnostic serum samples, this study identified markers with good discrimination for the lag-time of 0–9 months. However, the discrimination was low in blood samples collected more than 9 months prior to diagnosis, and none of the markers showed major improvement in discrimination when added to CA125.

TidsskriftBritish Journal of Cancer
Udgave nummer9
Sider (fra-til)1301-1309
Antal sider9
StatusUdgivet - 2022
Eksternt udgivetJa

Bibliografisk note

Funding Information:
The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London-, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS)—Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra,-and the Catalan Institute of Oncology— ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (C864/A14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (MR/N003284/1, MC-UU 12015/ 1 and MC UU_00006/1to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford). (United Kingdom). Open Access funding enabled and organized by Projekt DEAL.

Funding Information:
We acknowledge the use of data and biological samples from the EPIC-Asturias cohort, PI Ram?n Quir?s, the EPIC-Bilthoven cohort, PI W. M. Monique Verschuren, the EPIC-France cohort, PI Gianluca Severi, the EPIC- Utrecht, PI Roel Vermeulen and the EPIC-Norfolk cohort, PI Nick Wareham. We thank the Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands and the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands, for their contribution and ongoing support to the EPIC Study. We are grateful for the continuous participation of our cohort participants?without their commitment, this work would not have been possible.

Publisher Copyright:
© 2022, The Author(s).

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