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

Trasias Mukama, Renée Turzanski Fortner, Verena Katzke, Lucas Cory Hynes, Agnese Petrera, Stefanie M. Hauck, Theron Johnson, Matthias Schulze, Catarina Schiborn, Agnetha Linn Rostgaard-Hansen, Anne Tjønneland, Kim Overvad, María José Sánchez Pérez, Marta Crous-Bou, María Dolores Chirlaque, Pilar Amiano, Eva Ardanaz, Eleanor L. Watts, Ruth C. Travis, Carlotta SacerdoteSara 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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1301-1309
JournalBritish Journal of Cancer
Volume126
Issue number9
Early online date2022
DOIs
Publication statusPublished - 2022

Subject classification (UKÄ)

  • Cancer and Oncology

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