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Upregulation of centromere protein F is linked to aggressive prostate cancers

Authors Göbel C, Özden C, Schroeder C, Hube-Magg C, Kluth M, Möller-Koop C, Neubauer E, Hinsch A, Jacobsen F, Simon R, Sauter G, Michl U, Pehrke D, Huland H, Graefen M, Schlomm T, Luebke AM

Received 15 February 2018

Accepted for publication 23 May 2018

Published 9 November 2018 Volume 2018:10 Pages 5491—5504


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4

Editor who approved publication: Dr Antonella D'Anneo

Cosima Göbel,1,* Cansu Özden,1,* Cornelia Schroeder,2 Claudia Hube-Magg,1 Martina Kluth,1 Christina Möller-Koop,1 Emily Neubauer,1 Andrea Hinsch,1 Frank Jacobsen,1 Ronald Simon,1 Guido Sauter,1 Uwe Michl,3 Dirk Pehrke,3,4 Hartwig Huland,3 Markus Graefen,3 Thorsten Schlomm,3,4 Andreas M Luebke1

1Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 2General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 3Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 4Department of Urology, Charité - Universitätsmedizin Berlin, Berlin, Germany

*These authors contributed equally to this work

Background: Centromere protein F (CENPF) is a key component of the kinetochore complex and plays a crucial role in chromosome segregation and cell cycle progression. Recent work suggests that CENPF upregulation is linked to aggressive tumor features in a variety of malignancies including prostate cancer.
Materials and methods:
Using a highly annotated tissue microarray, we analyzed CENPF protein expression from a cohort of 8,298 prostatectomized patients by immunohistochemistry to study its effect on prostate-specific antigen recurrence-free survival.
Results: CENPF overexpression was found in 53% of cancers, and was linked to higher Gleason grade, advanced pathological tumor stage, accelerated cell proliferation, and lymph node metastasis (p<0.0001, each). A comparison with other key molecular features accessible through the microarray revealed strong associations between CENPF overexpression and presence of erythroblast transformation-specific (ETS)-related gene (ERG) fusion as well as phosphatase and tensin homolog deletion (p<0.0001, each). CENPF overexpression was linked to early biochemical recurrence. A subset analysis revealed that this was driven by the ERG-negative subset (p<0.0001). This was independent of established preoperative and postoperative prognostic parameters in multivariate analyses.
Conclusion: The results of our study identify CENPF overexpression as an important mechanism and a potential biomarker for prostate cancer aggressiveness.

Keywords: CENPF, ERG, deletion, prostate cancer, tissue microarray, prognosis

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