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Diagnosing and staging epithelial ovarian cancer by serum glycoproteomic profiling

  • Chirag Dhar,
  • Prasanna Ramachandran,
  • Gege Xu,
  • Chad Pickering,
  • Tomislav Čaval,
  • Maurice Wong,
  • Rachel Rice,
  • Bo Zhou,
  • Apoorva Srinivasan,
  • Paul Aiyetan,
  • Chih-Wei Chu,
  • Kaitlyn Moser,
  • Thomas J. Herzog,
  • Alexander Babatunde Olawaiye,
  • Francis Jacob,
  • Daniel Serie,
  • Klaus Lindpaintner,
  • Flavio Schwarz

摘要

Background

There is a need for diagnostic tests for screening, triaging and staging of epithelial ovarian cancer (EOC). Glycoproteomics of blood samples has shown promise for biomarker discovery.

Methods

We applied glycoproteomics to serum of people with EOC or benign pelvic masses and healthy controls. A total of 653 analytes were quantified and assessed in multivariable models, which were tested in an independent cohort. Additionally, we analyzed glycosylation patterns in serum markers and in tissues.

Results

We identified a biomarker panel that distinguished benign lesions from EOC with sensitivity and specificity of 83.5% and 90.1% in the training set, and of 86.7 and 86.7% in the test set, respectively. ROC analysis demonstrated strong performance across a range of cutoffs. Fucosylated multi-antennary glycopeptide markers were higher in late-stage than in early-stage EOC. A comparable pattern was found in late-stage EOC tissues.

Conclusions

Blood glycopeptide biomarkers have the potential to distinguish benign from malignant pelvic masses, and early- from late-stage EOC. Glycosylation of circulating and tumor tissue proteins may be related. This study supports the hypothesis that blood glycoproteomic profiling can be used for EOC diagnosis and staging and it warrants further clinical evaluation.