Small integrin-binding proteins as serum markers for prostate cancer detection.
OBJECTIVE
The small integrin-binding ligand N-linked glycoprotein (SIBLING) gene family includes bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), matrix extracellular phosphoglycoprotein (MEPE), and osteopontin (OPN). Previous studies have separately reported elevated expression of BSP, OPN, or DSPP in prostate tumor paraffin sections. We hypothesized that SIBLINGs may be informative serum markers for subjects with prostate cancer.


METHODS
Expression levels of SIBLINGs in biopsies of normal tissue and tumors from prostate were determined by cDNA array and by immunohistochemical staining with monoclonal antibodies. Competitive ELISAs for measuring total BSP, DSPP, MEPE, and OPN were applied to a test group of 102 subjects with prostate cancer and 110 normal subjects and a validation group of 90 subjects.


RESULTS
BSP, DMP1, DSPP, and OPN exhibited elevated mRNA expression and protein levels in biopsies. BSP, DSPP, and OPN were elevated in serum from prostate cancer subjects, with serum DSPP exhibiting the greatest difference, yielding an area under the receiver operator characteristic curve value of 0.98. Serum BSP and OPN levels were significantly elevated only in late stages, whereas DSPP was significantly elevated at all stages. Optimal serum value cutoff points derived for BSP, OPN, and DSPP were applied as a validation test to a new group of 90 subjects and DSPP yielded a sensitivity of 90% and a specificity of 100%.


CONCLUSIONS
Of the SIBLING gene family members, DSPP appears to be a strong candidate for use in serum assays for prostate cancer detection.
Jain
Alka
A
Division of Geriatric Medicine & Gerontology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
McKnight
Dianalee A
DA
Fisher
Larry W
LW
Humphreys
Elizabeth B
EB
Mangold
Leslie A
LA
Partin
Alan W
AW
Fedarko
Neal S
NS
D015415:Biomarkers / Q000032:analysis / Q000097:blood / Q000378:metabolism; D001798:Blood Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000032:analysis / Q000235:genetics; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D011485:Protein Binding; D012333:RNA, Messenger / Q000032:analysis; D012680:Sensitivity and Specificity
D015415:Biomarkers; D001798:Blood Proteins; D006023:Glycoproteins; D016023:Integrins; D012333:RNA, Messenger