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Changes in the expression of plasma proteins associated with thrombosis in BRCA1 mutation carriers

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Abstract

Purpose

Although BRCA1 gene mutations have been associated with breast cancer, BRCA1 mutations have been also involved in other functions. Thrombosis and coagulation are novel mechanisms recently associated with cancer. The aims of the present study were (a) to evaluate, using proteomics, if BRCA1 mutation carriers have a different plasma proteins expression related to thrombosis and coagulation profile than non-mutant BRCA1 women and (b) to analyze if the expression of these proteins may be different among BRCA1 mutation carriers with and without breast cancer.

Methods

Proteomic study was based on 2-dimensional electrophoresis and mass spectrometry. The study was performed in 10 BRCA1 non-mutant controls and 21 women with BRCA1 mutations (with breast cancer (n = 8) and breast cancer-free (n = 13)), all of them free of family history or diagnosis of ovarian cancer.

Results

Proteomic study showed that fibrinogen gamma chain isotypes 2 and 3, serotransferrin isotype 4, and convertase C3/C5 isotypes 1–5 were significantly increased in plasma from BRCA1 mutation carriers with respect to BRCA1 non-mutant controls. Plasma levels of alpha-1 antitrypsin isotypes 2–5, apolipoprotein A-IV, and vitamin D-binding protein isotypes 1 and 2 were significantly reduced in BRCA1 mutation carriers with respect to non-mutant controls. Only apolipoprotein A-IV plasma levels were significantly higher in cancer-free BRCA1 mutations carriers compared with BRCA1 mutations carriers who developed breast cancer.

Conclusion

It is suggested that independently of breast cancer generation, BRCA1-encoded gene alterations are associated with changes in the expression of circulating proteins associated with thrombosis and coagulation.

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Acknowledgments

This work has been supported by a grant from Oncology Spanish Society, Fondos de Investigaciones de la Seguridad Social (Redes Temáticas de Cooperación Red Heracles RD06/0009010 and Redes Temáticas Investigación y Cooperación en Cancer RD06/0020/0021). Petra J. Mateos-Cáceres is staff of Fundación para la Investigación Biomédica del Hospital Clínico San Carlos. José J Zamorano-León is staff of Red Heracles (Redes Temáticas de Cooperación Red Heracles RD06/0009/010). We thank Begoña Larrea for secretarial assistance.

Conflict of interest

All authors declare no conflicts of interest with respect to the manuscript entitled “Changes in the expression of plasma proteins associated with thrombosis in BRCA1 mutation carriers.”

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Authors and Affiliations

  1. Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), C/Profesor Martín Lagos, s/n, 28040, Madrid, Spain

    Ana Custodio, Trinidad Caldés, Miguel de la Hoya, Elena Olivera, Javier Puente, Eduardo Díaz-Rubio & Pedro Pérez-Segura

  2. Cardiovascular Research Unit of Cardiology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), C/Profesor Martín Lagos, s/n, 28040, Madrid, Spain

    Antonio J. López-Farré, José J. Zamorano-León, Petra J. Mateos-Cáceres & Carlos Macaya

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  1. Ana Custodio
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  2. Antonio J. López-Farré
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  3. José J. Zamorano-León
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  11. Pedro Pérez-Segura
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Correspondence to Pedro Pérez-Segura.

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Custodio, A., López-Farré, A.J., Zamorano-León, J.J. et al. Changes in the expression of plasma proteins associated with thrombosis in BRCA1 mutation carriers. J Cancer Res Clin Oncol 138, 867–875 (2012). https://doi.org/10.1007/s00432-012-1161-y

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