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Clinical relevance of gene expression in localized and metastatic prostate cancer exemplified by FABP5

  • K. Nitschke
  • P. Erben
  • F. Waldbillig
  • A. Abdelhadi
  • C.-A. Weis
  • M. Gottschalt
  • S. Wahby
  • P. Nuhn
  • M. Boutros
  • M. S. Michel
  • J. von Hardenberg
  • T. S. WorstEmail author
Topic Paper
  • 40 Downloads

Abstract

Purpose

Fatty acid-binding protein 5 (FABP5), a transport protein for lipophilic molecules, has been proposed as protein marker in prostate cancer (PCa). The role of FABP5 gene expression is merely unknown.

Methods

In two cohorts of PCa patients who underwent radical prostatectomy (n = 40 and n = 57) and one cohort of patients treated with palliative transurethral resection of the prostate (pTUR-P; n = 50) FABP5 mRNA expression was analyzed with qRT-PCR. Expression was correlated with clinical parameters. BPH tissue samples served as control. To independently validate findings on FABP5 expression, three microarray and sequencing datasets were reanalyzed (MSKCC 2010 n = 216; TCGA 2015 n = 333; mCRPC, Nature Medicine 2016 n = 114). FABP5 expression was correlated with ERG-fusion status, TCGA subtypes, cancer driver mutations and the expression of druggable downstream pathway components.

Results

FABP5 was overexpressed in PCa compared to BPH in the cohorts analyzed by qRT-PCR (radical prostatectomy p = 0.003, p = 0.010; pTUR-P p = 0.002). FABP5 expression was independent of T stage, Gleason Score, nodal status and PSA level. FABP5 overexpression was associated with the absence of TMPRSS2:ERG fusion (p < 0.001 in TCGA and MSKCC). Correlation with TCGA subtypes revealed FABP5 overexpression to be associated with SPOP and FOXA1 mutations. FABP5 was positively correlated with potential drug targets located downstream of FABP5 in the PPAR-signaling pathway.

Conclusion

FABP5 overexpression is frequent in PCa, but seems to be restricted to TMPRESS2:ERG fusion-negative tumors and is associated with SPOP and FOXA1 mutations. FABP5 overexpression appears to be indicative for increased activity in PPAR signaling, which is potentially druggable.

Keywords

FABP5 ERG ERG fusion Prostate cancer Expression Molecular subtypes 

Abbreviations

PCa

Prostate cancer

mCRPC

Metastatic castration-resistant prostate cancer

IHC

Immunohistochemistry

IQR

Interquartile range

BPH

Benign prostatic hyperplasia

pTUR-P

Palliative transurethral resection of the prostate

Notes

Acknowledgements

The project was funded by the B. Braun Stiftung (Melsungen, Germany). TSW was supported by a Ferdinand Eisenberger scholarship of the German Society of Urology.

Author contributions

KN: qRT-PCR experiments, data analysis, data collection, manuscript writing. PE: data analysis, manuscript writing. FW: qRT-PCR experiments, data analysis, data collection. AA: qRT-PCR experiments, data analysis. C-AW: tissue fixation, embedding, sectioning, staining and image acquisition. MG: tissue fixation, embedding, sectioning, staining and image acquisition. SW: qRT-PCR experiments. PN: project planning, manuscript writing. MB: project planning. MSM: project planning. JH: scientific advice, manuscript writing. TSW: project development, data collection, data analysis, manuscript writing.

Funding

This work was funded by the B. Braun Foundation (Melsungen, Germany). The funding sponsor had no role in the design of the study, in the collection, analysis or interpretation of the data, in the preparation of the manuscript and in the decision to publish the results.

Compliance with ethical standards

Conflict of interest

All authors declare no conflict of interest.

Ethical approval

The study includes data and tissue from human participants in a retrospective study (ethics approval 2013-845R-MA, 2014-592 N-MA).

Informed consent

All patients gave informed consent for participation. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Supplementary material

345_2019_2651_MOESM1_ESM.pdf (338 kb)
Supplementary material 1 (PDF 338 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • K. Nitschke
    • 1
  • P. Erben
    • 1
  • F. Waldbillig
    • 1
  • A. Abdelhadi
    • 1
  • C.-A. Weis
    • 2
  • M. Gottschalt
    • 2
  • S. Wahby
    • 1
  • P. Nuhn
    • 1
  • M. Boutros
    • 3
  • M. S. Michel
    • 1
  • J. von Hardenberg
    • 1
  • T. S. Worst
    • 1
    • 3
    Email author
  1. 1.Department of Urology, Medical Faculty MannheimUniversity of HeidelbergMannheimGermany
  2. 2.Department of Pathology, Medical Faculty MannheimUniversity of HeidelbergMannheimGermany
  3. 3.Department of Signaling and Functional GenomicsGerman Cancer Research Center (DKFZ)HeidelbergGermany

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