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67th Annual Meeting Abstracts
Small Integrin Binding Proteins as Serum Markers for Prostate Cancer Detection
Alan W Partin1, *Alka Jain1, *Leslie Mangold1, *Elizabeth Humphreys1, *Larry Fisher2, *Neal Fedarko1
1The Johns Hopkins School of Medicine, Baltimore, MD;2National Institutes of Health, Bethesda, MD
Introduction: The SIBLING (Small Integrin Binding LIgand N-linked Glycoprotein) 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 markers for prostate cancer.
Methods: Expression levels of SIBLINGs in biopsy normal tissue and tumor were determined by cDNA array and by immunohistochemistry. Competitive ELISAs for total BSP, DSPP, MEPE and OPN were applied to a group of 102 subjects with prostate cancer and 110 normal subjects and a validation group of 90 subjects.
Results: The SIBLINGs 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, while DSPP was significantly elevated at all stages. The elevated level of DSPP in serum was confirmed by SDS PAGE/Western blot analysis. Optimal serum value cut-off 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%.
Conclusion: Of the SIBLING gene family members, DSPP appears to be a strong candidate for use in serum assays for prostate cancer detection.
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