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


CONCLUSIONS
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.
Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
Ana
A
Custodio
Antonio J
AJ
López-Farré
José J
JJ
Zamorano-León
Petra J
PJ
Mateos-Cáceres
Carlos
C
Macaya
Trinidad
T
Caldés
Miguel
M
de la Hoya
Elena
E
Olivera
Javier
J
Puente
Eduardo
E
Díaz-Rubio
Pedro
P
Pérez-Segura
D000328:Adult; D001777:Blood Coagulation / Q000235:genetics; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019398:Genes, BRCA1; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D020543:Proteome / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D013927:Thrombosis / Q000097:blood / Q000235:genetics / Q000378:metabolism*
D001798:Blood Proteins; D020543:Proteome