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

Mukama, Trasias ; Fortner, Renée Turzanski ; Katzke, Verena ; Hynes, Lucas Cory ; Petrera, Agnese ; Hauck, Stefanie M. ; Johnson, Theron ; Schulze, Matthias ; Schiborn, Catarina and Rostgaard-Hansen, Agnetha Linn , et al. (2022) In British Journal of Cancer 126(9). p.1301-1309
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,... (More)

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.

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@article{6fd53ff2-c965-4093-b3a6-a533a67787b9,
  abstract     = {{<p>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 &gt;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.</p>}},
  author       = {{Mukama, Trasias and Fortner, Renée Turzanski and Katzke, Verena and Hynes, Lucas Cory and Petrera, Agnese and Hauck, Stefanie M. and Johnson, Theron and Schulze, Matthias and Schiborn, Catarina and Rostgaard-Hansen, Agnetha Linn and Tjønneland, Anne and Overvad, Kim and Pérez, María José Sánchez and Crous-Bou, Marta and Chirlaque, María Dolores and Amiano, Pilar and Ardanaz, Eva and Watts, Eleanor L. and Travis, Ruth C. and Sacerdote, Carlotta and Grioni, Sara and Masala, Giovanna and Signoriello, Simona and Tumino, Rosario and Gram, Inger T. and Sandanger, Torkjel M. and Sartor, Hanna and Lundin, Eva and Idahl, Annika and Heath, Alicia K. and Dossus, Laure and Weiderpass, Elisabete and Kaaks, Rudolf}},
  issn         = {{0007-0920}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{1301--1309}},
  publisher    = {{Nature Publishing Group}},
  series       = {{British Journal of Cancer}},
  title        = {{Prospective evaluation of 92 serum protein biomarkers for early detection of ovarian cancer}},
  url          = {{http://dx.doi.org/10.1038/s41416-021-01697-z}},
  doi          = {{10.1038/s41416-021-01697-z}},
  volume       = {{126}},
  year         = {{2022}},
}