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Clinical relevance of cytoskeleton associated proteins for ovarian cancer

  • Original Article – Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Ovarian cancer has a high mortality rate and up to now no reliable molecular prognostic biomarkers have been established. During malignant progression, the cytoskeleton is strongly altered. Hence we analyzed if expression of certain cytoskeleton-associated proteins is correlated with clinical outcome of ovarian cancer patients.

Methods

First, in silico analysis was performed using the cancer genome atlas (TCGA), the human expression atlas and Pubmed. Selected candidates were validated on 270 ovarian cancer patients by qRT-PCR and/or by western blotting.

Results

In silico analysis revealed that mRNAs of 214 cytoskeleton-associated proteins are detectable in ovarian cancer tissue. Among these, we selected 17 proteins that participate in cancer disease progression and cytoskeleton modulation: KIF14, KIF20A, KIF18A, ASPM, CEP55, DLGAP5, MAP9, EB1, KATNA1, DIAPH1, ANLN, SCIN, CCDC88A, FSCN1, GSN, VASP and CDC42. The first ten candidates interact with microtubules (MTs) and the others bind to actin filaments. Validation on clinical samples of ovarian cancer patients revealed that the expression levels of DIAPH1, EB1, KATNA1, KIF14 and KIF18A significantly correlated with clinical and histological parameters of ovarian cancer. High DIAPH1, EB1, KATNA1 and KIF14 protein levels were associated with increased overall survival (OAS) of ovarian cancer patients, while high DIAPH1 and EB1 protein levels were also associated with low differentiation of respective tumors (G2/3). Moreover, DIAPH1 was the only protein, whose expression significantly correlated with increased recurrence-free interval (RFI).

Conclusion

Mainly the expression levels of the MT-associated proteins analyzed in this study, correlated with prolonged survival of ovarian cancer patients. From > 200 genes initially considered, 17 cytoskeletal proteins are involved in cancer progression according to the literature. Among these, four proteins significantly correlated with improved survival of ovarian cancer patients.

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Funding

This project was financially supported by initial financing of the UKE.

Author information

Author notes

  1. Leticia Oliveira-Ferrer and Sabine Windhorst contribute equally to the manuscript.

Authors and Affiliations

  1. Department of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Johanna Schiewek & Sabine Windhorst

  2. Institute of Anatomy and Experimental Morphology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Udo Schumacher & Tobias Lange

  3. Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Simon A. Joosse, Harriet Wikman & Klaus Pantel

  4. DFG Emmy Noether Group ‘Neuronal Protein Transport’, Center for Molecular Neurobiology, ZMNH, University Medical Center Hamburg-Eppendorf, 20251, Hamburg, Germany

    Marina Mikhaylova

  5. Department of Molecular Neurogenetics, Center for Molecular Neurobiology, ZMNH, University Medical Center Hamburg-Eppendorf, Falkenried 94, 20251, Hamburg, Germany

    Matthias Kneussel

  6. Institute for Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany

    Stefan Linder

  7. Department of Gynecology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Barbara Schmalfeldt & Leticia Oliveira-Ferrer

Authors
  1. Johanna Schiewek
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  2. Udo Schumacher
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  3. Tobias Lange
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  4. Simon A. Joosse
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  5. Harriet Wikman
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  6. Klaus Pantel
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  7. Marina Mikhaylova
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  8. Matthias Kneussel
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  9. Stefan Linder
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  10. Barbara Schmalfeldt
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  11. Leticia Oliveira-Ferrer
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  12. Sabine Windhorst
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Corresponding author

Correspondence to Sabine Windhorst.

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Conflict of interest

All authors declare that there is no competing interest.

Ethical standards

Patients gave their written approvals for examining tissue samples and reviewing their medical records according to our investigational review board and ethics committee guidelines (#190504).

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Schiewek, J., Schumacher, U., Lange, T. et al. Clinical relevance of cytoskeleton associated proteins for ovarian cancer. J Cancer Res Clin Oncol 144, 2195–2205 (2018). https://doi.org/10.1007/s00432-018-2710-9

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  • DOI: https://doi.org/10.1007/s00432-018-2710-9

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