Upregulation of centromere protein F is linked to aggressive prostate cancers
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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