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Association of circulating free and total oxysterols in breast cancer patients

  • Nina Sophia Decker ORCID logo , Theron Johnson ORCID logo , Sabine Behrens , Nadia Obi , Rudolf Kaaks , Jenny Chang-Claude and Renée Turzanski Fortner ORCID logo EMAIL logo
Published/Copyright: November 8, 2022
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 61 Issue 2

Abstract

Objectives

Oxysterols, a family of oxidized cholesterol derivates, are of increasing interest due to their role in cancer development and progression. Some oxysterols are estrogen receptor modulators and thus of particular interest in breast cancer research. In human studies, two forms of circulating oxysterols are commonly evaluated: “free” (unesterified) and “total” (esterified and unesterified). However, associations between free and total oxysterols are not well established. We addressed this knowledge gap in a pilot study by evaluating correlations between the free and the total form of each of the circulating oxysterols (free vs. total), and pairwise associations within the panel of total oxysterols (total vs. total) and the panel of free oxysterols (free vs. free).

Methods

Concentrations of oxysterols and other non-cholesterol sterols were quantified in blood samples of 27 breast cancer patients from the MARIE breast cancer patient cohort using liquid chromatography mass spectrometry. We used Spearman rank correlations to assess associations. Overall, 12 oxysterols (including 27-hydroxycholesterol (HC), 25-HC, 24S-HC, 7a-HC, 5a6a-epoxycholesterol) and five sterols (including lanosterol and desmosterol) were analyzed.

Results

Strong correlations (r≥0.82) were observed for seven circulating free and total oxysterols/sterols. The free and total form of 27-HC (r=0.63), 25-HC (r=0.54), and two more oxysterols were weaker correlated. Correlation patterns in the panel of total oxysterols/sterols and the panel of free oxysterols/sterols were similar.

Conclusions

These findings demonstrate that concentrations of most free and total oxysterols/sterols are strongly correlated. We provide further insight into the interrelationships between oxysterols in breast cancer patients.

Keywords: 27-hydroxycholesterol; breast cancer; comparability; esterification; oxysterols; sterols
Corresponding author: Dr. Renée Turzanski Fortner, Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; and Cancer Registry of Norway, Ullernchausseen 64, 0379 Oslo, Norway, E-mail:

Funding source: U.S. Army Medical Research and Material Command Fort Detrick, Maryland 21702-5012 http://dx.doi.org/10.13039/100016156

Award Identifier / Grant number: W81XWH-19-1-0786 (Fortner)

Acknowledgments

We are grateful to all the MARIE study participants for their contribution and the interviewers who collected the data. We thank Muhabbet Celik for sample preparation and sample coordination, and the biocrates service lab team for their expert advice in interpreting the oxysterol data. We express gratitude to Dieter Flesch-Janys for his invaluable contributions to the MARIE projects as former PI of the Hamburg study region. The MARIE study was funded by the German Cancer Aid (Deutsche Krebshilfe e.V.; Grant numbers 70-2892-BR I, 108419 and 108253, 110826 and 110828), the German Cancer Research Center (DKFZ), and the Hamburg Cancer Society.

  1. Research funding: This work was supported by the U.S. Army Medical Research and Material Command Fort Detrick, Maryland 21702-5012 under Award No. W81XWH-19-1-0786 (Fortner). The funding organization played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

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

  5. Ethical approval: The research related to human use has complied with all the relevant national regulations, institutional policies, and in accordance with the tenets of the Helsinki Declaration, and has been approved by the authors’ Institutional Review Board or equivalent committee (Ethics Committees of the University of Heidelberg, S-685/2019).

  6. Data availability: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2022-0705).

Received: 2022-04-01
Accepted: 2022-10-25
Published Online: 2022-11-08
Published in Print: 2023-01-27

© 2022 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2022-0705
Keywords for this article
27-hydroxycholesterol; breast cancer; comparability; esterification; oxysterols; sterols

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Standardization and harmonization in laboratory medicine: not only for clinical chemistry measurands
  4. Mini Review
  5. The effect of the immunoassay curve fitting routine on bias in troponin
  6. Opinion Papers
  7. An overview of the most important preanalytical factors influencing the clinical performance of SARS-CoV-2 antigen rapid diagnostic tests (Ag-RDTs)
  8. Time to address quality control processes applied to antibody testing for infectious diseases
  9. Perspectives
  10. Definition and application of performance specifications for measurement uncertainty of 23 common laboratory tests: linking theory to daily practice
  11. The gaps between the new EU legislation on in vitro diagnostics and the on-the-ground reality
  12. General Clinical Chemistry and Laboratory Medicine
  13. Second-generation Elecsys cerebrospinal fluid immunoassays aid diagnosis of early Alzheimer’s disease
  14. Evaluation of the interchangeability between the new fully-automated affinity chrome-mediated immunoassay (ACMIA) and the Quantitative Microsphere System (QMS) with a CE-IVD-certified LC-MS/MS assay for therapeutic drug monitoring of everolimus after solid organ transplantation
  15. Quantitative detection of anti-PLA2R antibodies targeting different epitopes and its clinical application in primary membranous nephropathy
  16. Reference Values and Biological Variations
  17. A zlog-based algorithm and tool for plausibility checks of reference intervals
  18. Harmonization of indirect reference intervals calculation by the Bhattacharya method
  19. Red blood cell parameters in early childhood: a prospective cohort study
  20. Cancer Diagnostics
  21. Association of circulating free and total oxysterols in breast cancer patients
  22. Effect of short-term storage of blood samples on gene expression in lung cancer patients
  23. Infectious Diseases
  24. Operation Moonshot: rapid translation of a SARS-CoV-2 targeted peptide immunoaffinity liquid chromatography-tandem mass spectrometry test from research into routine clinical use
  25. Seroprevalence of SARS-CoV-2 antibodies in Italy in newborn dried blood spots
  26. Positivization time of a COVID-19 rapid antigen self-test predicts SARS-CoV-2 viral load: a proof of concept
  27. New insights into SARS-CoV-2 Lumipulse G salivary antigen testing: accuracy, safety and short TAT enhance surveillance
  28. Preanalytical stability of SARS-CoV-2 anti-nucleocapsid antibodies
  29. Prognostic value of procalcitonin in cancer patients with coronavirus disease 2019
  30. 24/7 workflow for bloodstream infection diagnostics in microbiology laboratories: the first step to improve clinical management
  31. Diagnostic performance of machine learning models using cell population data for the detection of sepsis: a comparative study
  32. Diagnostic value of procalcitonin, hypersensitive C-reactive protein and neutrophil-to-lymphocyte ratio for bloodstream infections in pediatric tumor patients
  33. Letters to the Editor
  34. Pseudohyponatremia: interference of hyperglycemia on indirect potentiometry
  35. Ligand binding assay-related underestimation of 25-hydroxyvitamin D in pregnant women exaggerates the prevalence of vitamin D insufficiency
  36. Urokinase-type plasminogen activator soluble receptor (suPAR) assay in clinical routine: evaluation one year after its introduction in the high automation corelab of the A. Gemelli hospital
  37. Is this a true lambda free light chain?
  38. Effect of various blood collection tubes on serum lithium and other electrolytes: our perspective from a tertiary healthcare institute
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