A predictive and prognostic model for surgical outcome and prognosis in ovarian cancer computed by clinico-pathological and serological parameters (CA125, HE4, mesothelin)

Clin Chem Lab Med. 2023 Oct 11;62(3):530-539. doi: 10.1515/cclm-2023-0314. Print 2024 Feb 26.

Abstract

Objectives: Numerous prognostic models have been proposed for ovarian cancer, extending from single serological factors to complex gene-expression signatures. Nonetheless, these models have not been routinely translated into clinical practice. We constructed a robust and readily calculable model for predicting surgical outcome and prognosis of ovarian cancer patients by exploiting commonly available clinico-pathological factors and three selected serum parameters.

Methods: Serum CA125, human epididymis protein 4 (HE4) and mesothelin (MSL) were quantified by Lumipulse® G chemiluminescent enzyme immunoassay (Fujirebio) in a total of 342 serum samples from 190 ovarian cancer patients, including 152 paired pre- and post-operative samples.

Results: Detection of pre-operative HE4 and CA125 was the optimal marker combination for blood-based prediction of surgical outcome (AUC=0.86). We constructed a prognostic model, computed by serum levels of pre-operative CA125, post-operative HE4, post-operative MSL and surgical outcome. Prognostic performance of our model was superior to any of these parameters alone and was independent from BRCA1/2 mutational status. We subsequently transformed our model into a prognostic risk index, stratifying patients as "lower risk" or "higher risk". In "higher risk" patients, relapse or death was predicted with an AUC of 0.89 and they had a significantly shorter progression free survival (HR: 9.74; 95 % CI: 5.95-15.93; p<0.0001) and overall survival (HR: 5.62; 95 % CI: 3.16-9.99; p<0.0001) compared to "lower risk" patients.

Conclusions: We present a robust predictive/prognostic model for ovarian cancer, which could readily be implemented into routine diagnostics in order to identify ovarian cancer patients at high risk of recurrence.

Keywords: CA125; HE4; mesothelin; ovarian cancer; prognostic model.

MeSH terms

  • BRCA1 Protein*
  • BRCA2 Protein
  • Biomarkers, Tumor
  • CA-125 Antigen
  • Carcinoma, Ovarian Epithelial
  • Female
  • Humans
  • Mesothelin
  • Neoplasm Recurrence, Local
  • Ovarian Neoplasms* / diagnosis
  • Ovarian Neoplasms* / metabolism
  • Ovarian Neoplasms* / surgery
  • Prognosis
  • Proteins
  • Treatment Outcome

Substances

  • BRCA1 protein, human
  • BRCA1 Protein
  • Mesothelin
  • Proteins
  • Biomarkers, Tumor
  • BRCA2 protein, human
  • BRCA2 Protein
  • CA-125 Antigen