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

  • Daniel Martin Klotz ORCID logo , Theresa Link , Pauline Wimberger and Jan Dominik Kuhlmann EMAIL logo
Published/Copyright: October 11, 2023
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 62 Issue 3

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: ovarian cancer; prognostic model; CA125; HE4; mesothelin
Corresponding author: Prof. Dr. Jan Dominik Kuhlmann, Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany; National Center for Tumour Diseases (NCT), Dresden, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany; and German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany, Phone: ++49 351 458 2434, Fax: ++49 351 458 5844, E-mail:

Funding source: Fujirebio Europe, Gent, Belgium

Acknowledgments

The authors want to thank Dr. M. Stevense (TU Dresden) for language editing. We further thank L. Vernoux (Fujirebio) for excellent statistical and technical assistance.

  1. Research ethics: The study was approved by the Local Research Ethics Committee at the Technische Universität Dresden, Germany (file number: EK74032013) and was performed in accordance with good clinical practice guidelines, national laws and the Declaration of Helsinki.

  2. Informed consent: Informed consent was obtained from all individuals included in this study.

  3. Author contributions: JDK, DMK, PW, TL made substantial contributions to the conception and design of the study. JDK and DMK contributed to the experimental work or to the acquisition of data and to the analysis/interpretation of the results. JDK and DMK, TL and PW were involved in drafting the manuscript, creating figures or revising the manuscript. All authors read and approved the manuscript in its final version. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Competing interests: COI disclosures have been uploaded for each author.

  5. Research funding: The study was supported by Fujirebio Europe, Gent, Belgium by supplying Lumipulse® G chemiluminescent enzyme immunoassays.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2023-0314).

Received: 2023-03-28
Accepted: 2023-09-18
Published Online: 2023-10-11
Published in Print: 2024-02-26

© 2023 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2023-0314
Keywords for this article
ovarian cancer; prognostic model; CA125; HE4; mesothelin

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Unraveling the mystery of blood groups and COVID-19
  4. Reviews
  5. Serum hepcidin levels in chronic liver disease: a systematic review and meta-analysis
  6. Platelet distribution width (PDW) as a significant correlate of COVID-19 infection severity and mortality
  7. Mini Reviews
  8. ABO blood group-related mechanism of infection of SARS-CoV-2: an overview of systematic reviews
  9. Opinion Paper
  10. Personalized laboratory medicine in the digital health era: recent developments and future challenges
  11. Guidelines and Recommendations
  12. Algorithm of differential diagnosis of anemia involving laboratory medicine specialists to advance diagnostic excellence
  13. General Clinical Chemistry and Laboratory Medicine
  14. Rescaling creatinine makes GFR estimation equations generally applicable across populations – validation results for the Lund-Malmö equation in a French cohort of sub-Saharan ancestry
  15. Periodic verification of results’ comparability between several analyzers: experience in the application of the EP31-A-IR guideline
  16. Machine learning to optimize cerebrospinal fluid dilution for analysis of MRZH reaction
  17. Diagnostic performance of automated red cell parameters in predicting bone marrow iron stores
  18. Reliability of hemoglobin A2 value as measured by the Premier Resolution system for screening of β-thalassemia carriers
  19. Amino acid sequence homology of monoclonal serum free light chain dimers and tissue deposited light chains in AL amyloidosis: a pilot study
  20. Development of high-performance point-of-care aqueous VEGF detection system and proof-of-concept validation in RVO patients
  21. Detection rate of IGF-1 variants and their implication to protein binding: study of over 240,000 patients
  22. Analysis of a second-tier test panel in dried blood spot samples using liquid chromatography-tandem mass spectrometry in Catalonia’s newborn screening programme
  23. Targeted quantitative lipidomic uncovers lipid biomarkers for predicting the presence of compensated cirrhosis and discriminating decompensated cirrhosis from compensated cirrhosis
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  25. Establishment of reference intervals for free light chains and immunoglobulins in Saudi population
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  31. Infectious Diseases
  32. Monocyte distribution width as an early predictor of short-term outcome in adult patients with sepsis
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