Correlated expression of CD47 and SIRPA in bone marrow and in peripheral blood predicts recurrence in breast cancer patients.
OBJECTIVE
CD47 plays a variety of roles in intercellular signaling. Herein, we focused on the clinicopathologic significance of CD47 expression in human breast cancer. Our data suggest that the correlation between CD47 and signal regulatory protein α (SIRPA) expression may play a key role in the progression of breast cancer.


METHODS
Quantitative real-time PCR was used to evaluate CD47 mRNA and SIRPA mRNA expression in bone marrow and in peripheral blood from 738 cases of breast cancer.


RESULTS
In patients with high levels of CD47 expression in the bone marrow, survival was significantly poorer compared with patients with low levels of CD47 expression [disease-free survival (DFS), P = 0.0035; overall survival (OS), P = 0.015]. Furthermore, high CD47 expression group in a multivariate analysis showed significance as an independent variable for poorer prognosis in DFS (P = 0.024). In the peripheral blood, however, high CD47 expression in patients was not an independent and significant prognostic factor for DFS and OS in a multivariate analysis. CD47 expression was strongly correlated with SIRPA expression in both the bone marrow (P < 0.0001) and peripheral blood (P < 0.0001) of breast cancer patients.


CONCLUSIONS
This is one of the first studies to show that a host factor in bone marrow confers prognostic importance. CD47 is an important biomarker in breast cancer, and functions as a prognostic factor for DFS. Moreover, we suggest that the poor prognosis of breast cancer patients with high expression of CD47 is due to an active CD47/SIRPA signaling pathway in circulating cells.
Nagahara
Makoto
M
Department of Surgery and Molecular Oncology, Medical Institute of Bioregulation, Kyushu University, Oita, Japan.
Mimori
Koshi
K
Kataoka
Akemi
A
Ishii
Hideshi
H
Tanaka
Fumiaki
F
Nakagawa
Tsuyoshi
T
Sato
Takanobu
T
Ono
Shinji
S
Sugihara
Kenichi
K
Mori
Masaki
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000943:Antigens, Differentiation / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D001773:Blood Cells / Q000378:metabolism* / Q000473:pathology; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D051928:CD47 Antigen / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D011379:Prognosis; D011971:Receptors, Immunologic / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D012008:Recurrence; D016019:Survival Analysis; D055815:Young Adult
D000943:Antigens, Differentiation; D051928:CD47 Antigen; C497894:CD47 protein, human; D011971:Receptors, Immunologic; C501920:SIRPA protein, human