Small integrin-binding proteins as serum markers for prostate cancer detection

Alka Jain, Dianalee A. McKnight, Larry W. Fisher, Elizabeth B. Humphreys, Leslie A. Mangold, Alan Wayne Partin, Neal S Fedarko

Research output: Contribution to journalArticle

Abstract

Purpose: 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 serumfromprostate cancer subjects, with serum DS PP 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%. Conclusion: Of the SIBLING gene family members, DSPP appears to be a strong candidate for use in serumassays for prostate cancer detection.

Original languageEnglish (US)
Pages (from-to)5199-5207
Number of pages9
JournalClinical Cancer Research
Volume15
Issue number16
DOIs
StatePublished - Aug 15 2009

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Integrin-Binding Sialoprotein
Integrins
Osteopontin
Prostatic Neoplasms
Carrier Proteins
Biomarkers
Dentin
Extracellular Matrix
Prostate
Glycoproteins
Serum
Ligands
Biopsy
dentin sialophosphoprotein
Neoplasms
Proteins
Oligonucleotide Array Sequence Analysis
Paraffin
Genes
Enzyme-Linked Immunosorbent Assay

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Small integrin-binding proteins as serum markers for prostate cancer detection. / Jain, Alka; McKnight, Dianalee A.; Fisher, Larry W.; Humphreys, Elizabeth B.; Mangold, Leslie A.; Partin, Alan Wayne; Fedarko, Neal S.

In: Clinical Cancer Research, Vol. 15, No. 16, 15.08.2009, p. 5199-5207.

Research output: Contribution to journalArticle

Jain, Alka ; McKnight, Dianalee A. ; Fisher, Larry W. ; Humphreys, Elizabeth B. ; Mangold, Leslie A. ; Partin, Alan Wayne ; Fedarko, Neal S. / Small integrin-binding proteins as serum markers for prostate cancer detection. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 16. pp. 5199-5207.
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abstract = "Purpose: 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 serumfromprostate cancer subjects, with serum DS PP 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{\%}. Conclusion: Of the SIBLING gene family members, DSPP appears to be a strong candidate for use in serumassays for prostate cancer detection.",
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AU - Jain, Alka

AU - McKnight, Dianalee A.

AU - Fisher, Larry W.

AU - Humphreys, Elizabeth B.

AU - Mangold, Leslie A.

AU - Partin, Alan Wayne

AU - Fedarko, Neal S

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N2 - Purpose: 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 serumfromprostate cancer subjects, with serum DS PP 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%. Conclusion: Of the SIBLING gene family members, DSPP appears to be a strong candidate for use in serumassays for prostate cancer detection.

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