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

Br J Cancer. 2022 May;126(9):1301-1309. doi: 10.1038/s41416-021-01697-z. Epub 2022 Jan 14.

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.

MeSH terms

  • ADAM Proteins / metabolism
  • Biomarkers, Tumor* / metabolism
  • Blood Proteins
  • CA-125 Antigen
  • Carcinoma, Ovarian Epithelial
  • Case-Control Studies
  • Early Detection of Cancer
  • Female
  • Folate Receptor 1
  • Humans
  • Membrane Proteins / metabolism
  • Ovarian Neoplasms* / metabolism
  • ROC Curve

Substances

  • Biomarkers, Tumor
  • Blood Proteins
  • CA-125 Antigen
  • FOLR1 protein, human
  • Folate Receptor 1
  • Membrane Proteins
  • ADAM Proteins
  • ADAM8 protein, human