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

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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.

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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

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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.

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.

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Authors and Affiliations

  1. Department of Urology, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany

    K. Nitschke, P. Erben, F. Waldbillig, A. Abdelhadi, S. Wahby, P. Nuhn, M. S. Michel, J. von Hardenberg & T. S. Worst

  2. Department of Pathology, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany

    C.-A. Weis & M. Gottschalt

  3. Department of Signaling and Functional Genomics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120, Heidelberg, Germany

    M. Boutros & T. S. Worst

Authors
  1. K. Nitschke
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  2. P. Erben
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  11. J. von Hardenberg
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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.

Corresponding author

Correspondence to T. S. Worst.

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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.

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Nitschke, K., Erben, P., Waldbillig, F. et al. Clinical relevance of gene expression in localized and metastatic prostate cancer exemplified by FABP5. World J Urol 38, 637–645 (2020). https://doi.org/10.1007/s00345-019-02651-8

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  • DOI: https://doi.org/10.1007/s00345-019-02651-8

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