Elevated Serum Bone Sialoprotein and Osteopontin in Colon,
Breast, Prostate, and Lung Cancer1
Neal S. Fedarko,2,3 Alka Jain,2
Abdullah Karadag, Matthew R. Van Eman, and
Larry W. Fisher
Division of Geriatrics, Department of Medicine, The Johns Hopkins
University School of Medicine, Baltimore, Maryland 21224 [N. S. F.,
A. J.], and Matrix Biochemistry Unit, Craniofacial and Skeletal
Diseases Branch, National Institute of Dental and Craniofacial
Research, NIH, Bethesda, Maryland 20892 [A. K., M. R. V. E.,
L. W. F.]
ABSTRACT
Purpose: Histological studies have shown that the two
sialoproteins, bone sialoprotein (BSP) and osteopontin
(OPN), are induced in multiple types of cancer. We have
recently found that these proteins are bound in serum to
complement factor H and that the complex must be dis-
rupted to generate free protein to measure their total levels.
We hypothesized that measuring total BSP and OPN levels
would provide informative markers for the detection of
cancer.
Experimental Design: As a proof of concept study, se-
rum from patients with diagnosed breast, colon, lung, or
prostate cancer (n 20 for each type) as well as normal
serum (n 77) were analyzed using competitive ELISAs
developed for BSP and OPN. Sensitivity, specificity, as well
as positive and negative predictive values were determined
for each sialoprotein and cancer type. The relationship be-
tween sensitivity and specificity was profiled by receiver
operating characteristic curves.
Results and Conclusions: Determined values for serum
BSP in ng/ml were 285 19 for prostate, 373 19 for colon,
318 18 for breast, 155 11 for lung cancer sera, and
154 13 for normal sera. Values of OPN in ng/ml were
653 39 for prostate, 449 22 for colon, 814 53 for
breast, 724 33 for lung, and 439 30 for normal sera. The
assays provide a high degree of sensitivity and specificity
that enables the detection of colon, breast, prostate, and lung
cancer.
INTRODUCTION
The family of secreted proteins, which we term SIBLINGs4
(1), contains
the integrin-