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. 2018 Nov 9:10:5491-5504.
doi: 10.2147/CMAR.S165630. eCollection 2018.

Upregulation of centromere protein F is linked to aggressive prostate cancers

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 Luebke  1
Affiliations

Upregulation of centromere protein F is linked to aggressive prostate cancers

Cosima Göbel et al. Cancer Manag Res. .

Abstract

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; prognosis; prostate cancer; tissue microarray.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Representative pictures of CENPF staining in (A) normal prostate glands (negative/weak) and in prostate cancer with (B) negative/weak, (C) moderate, and (D) strong staining intensity. Spot size 600 µm, 100× magnification. Abbreviation: CENPF, centromere protein F.
Figure 2
Figure 2
Association between CENPF staining level and clinical tumor phenotype. Abbreviations: CENPF, centromere protein F; FISH, fluorescence in situ hybridization; IHC, immunohistochemistry.
Figure 3
Figure 3
Association between CENPF staining and ERG expression by immunohistochemistry or TMPRSS2:ERG fusion by FISH. Abbreviations: CENPF, centromere protein F; ERG, erythroblast transformation-specific (ETS)-related gene; TMPRSS2, transmembrane protease, serine 2; FISH, fluorescence in situ hybridization.
Figure 4
Figure 4
Association between CENPF staining intensity and 10q23 (PTEN), 5q21 (CHD1), 6q15 (MAP3K7), and 3p13 (FOXP1) deletions in (A) all cancers, (B) the ERG-negative subset, and (C) the ERG-positive subset. Abbreviations: CENPF, centromere protein F; PTEN, phosphatase and tensin homolog; CHD1, chromodomain-helicase-DNA-binding protein 1; MAP3K7, mitogen-activated protein kinase kinase kinase 7; FOXP1, fork head box protein P1.
Figure 5
Figure 5
Ki67 labeling index is independently associated with the CENPF expression level and the Gleason grade. Abbreviation: CENPF, centromere protein F.
Figure 6
Figure 6
Association between CENPF expression and PSA recurrence after prostatectomy in (A) all cancers, (B) the ERG-negative subset, and (C) the ERG-positive subset. Abbreviations: CENPF, centromere protein F; PSA, prostate-specific antigen; ERG, erythroblast transformation-specific (ETS)-related gene.
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