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Serum follistatin in patients with prostate cancer metastatic to the bone

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Abstract

The clinical significance of circulating follistatin (FLST), an inhibitor of the multifunctional cytokine activin A (Act A), was investigated in patients with prostate cancer (PCa). The serum concentrations of this molecule were determined by an enzyme-linked immunosorbent assay (ELISA) in PCa patients with (M+) or without (M0) bone metastases, in patients with benign prostate hyperplasia (BPH) and in healthy subjects (HS). The effectiveness of FLST in detecting PCa patients with skeletal metastases was determined by the receiver operating characteristic (ROC) curve analysis. Serum FLST was significantly higher in PCa patients than in BPH patients (P = 0.001) or HS (P = 0.011). Conversely, in BPH patients, FLST levels resulted lower than in HS (P = 0.025). In cancer patients the serum concentrations of FLST significantly correlated with the presence of bone metastases (P = 0.0005) or increased PSA levels (P = 0.04). Interestingly, significant differences in the ratio between FLST and Act A serum concentrations (FLST/Act A) were observed between HS and BPH patients (P = 0.001) or PCa patients (P = 0.0005). Finally, ROC curve analysis, highlighted a sound diagnostic performance of FLST in detecting M+ patients (P = 0.0001). However, the diagnostic effectiveness of FLST did not result significantly superior to that of Act A or PSA. These findings suggest that FLST may be regarded as a potential, molecular target in the treatment of metastatic bone disease while its clinical role as soluble marker in the clinical management of PCa patients with bone metastases needs to be better defined.

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Abbreviations

Act A:

Activin A

ActRII:

Activin type II receptor

AUC:

Area under the curve

BMP-7:

Bone morphogenic protein-7

BPH:

Benign prostate hyperplasia

FLST:

Follistatin

FLST/Act A ratio:

Follistatin/Activin A ratio

ELISA:

Enzyme linked immunosorbent assay

HS:

Healthy subjects

MMP-2:

Matrix-metalloproteinase-2

M0:

Patients with confined disease

M+:

Patients with bone metastases

PCa:

Prostate cancer

PSA:

Prostate specific antigen

ROC curve:

Receiver operating characteristic curve

SCLC:

Small cell lung cancer

TGF-β:

Transforming growth factor-beta

VEGF:

Vascular endothelial growth factor

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Acknowledgments

This study was supported by funds from Ministry of Education, University and Research (MIUR) (Fondi Ateneo ex quota 60%).

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Correspondence to Gaetano Leto.

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Tumminello, F.M., Badalamenti, G., Fulfaro, F. et al. Serum follistatin in patients with prostate cancer metastatic to the bone. Clin Exp Metastasis 27, 549–555 (2010). https://doi.org/10.1007/s10585-010-9344-x

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  • DOI: https://doi.org/10.1007/s10585-010-9344-x

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