Autoantibodies, antigen-autoantibody complexes and antigens complement CA125 for early detection of ovarian cancer

Br J Cancer. 2024 Mar;130(5):861-868. doi: 10.1038/s41416-023-02560-z. Epub 2024 Jan 9.

Abstract

Background: Multiple antigens, autoantibodies (AAb), and antigen-autoantibody (Ag-AAb) complexes were compared for their ability to complement CA125 for early detection of ovarian cancer.

Methods: Twenty six biomarkers were measured in a single panel of sera from women with early stage (I-II) ovarian cancers (n = 64), late stage (III-IV) ovarian cancers (186), benign pelvic masses (200) and from healthy controls (502), and then split randomly (50:50) into a training set to identify the most promising classifier and a validation set to compare its performance to CA125 alone.

Results: Eight biomarkers detected ≥ 8% of early stage cases at 98% specificity. A four-biomarker panel including CA125, HE4, HE4 Ag-AAb and osteopontin detected 75% of early stage cancers in the validation set from among healthy controls compared to 62% with CA125 alone (p = 0.003) at 98% specificity. The same panel increased sensitivity for distinguishing early-stage ovarian cancers from benign pelvic masses by 25% (p = 0.0004) at 95% specificity. From 21 autoantibody candidates, 3 AAb (anti-p53, anti-CTAG1 and annt-Il-8) detected 22% of early stage ovarian cancers, potentially lengthening lead time prior to diagnosis.

Conclusion: A four biomarker panel achieved greater sensitivity at the same specificity for early detection of ovarian cancer than CA125 alone.

MeSH terms

  • Autoantibodies*
  • Biomarkers, Tumor
  • CA-125 Antigen
  • Female
  • Humans
  • Ovarian Neoplasms* / diagnosis
  • ROC Curve
  • Sensitivity and Specificity

Substances

  • Autoantibodies
  • CA-125 Antigen
  • Biomarkers, Tumor