Small Integrin-Binding Proteins as Serum Markers for Prostate Cancer Detection

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 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%. Conclusion: Of the SIBLING gene family members, DSPP appears to be a strong candidate for use in serum assays for prostate cancer detection. (Clin Cancer Res 2009;15(16):5199-207)

Bone turnover markers in serum and urine as diagnostic, prognostic and monitoring biomarkers of bone metastasis

“…However, BSP can be considered a general tumor marker rather than a typical bone biomarker since the concentrations increase in patients with locally confined prostate carcinoma as well [88,134]. This is apparently also the case for OPN as the other SIBLING protein discussed here [103].…”

Stability and degradation of fibroblast growth factor 23 (FGF23): the effect of time and temperature and assay type

“…Alternatively, long-term storage leads to denaturation and/or degradation of the proteins, which in turn generates more fragments containing available epitopes that are recognized by polyclonal antibodies (such as Immutopics), and generates a higher signal. This phenomenon of increased signal when where a rabbit polyclonal antibody recognized fragments of the protein in question whereas the monoclonal antibody did not [18]. Other factors that can affect levels during sample storage include prolonged contact of serum with erythrocytes leading to exchange of substances and either dilution or increase of concentration, hemolysis (again causing either dilution or increase concentration), and interference of hemoglobin in the measurement (specifically in the photometric quantification of constituents) [19].…”

Single-walled carbon nanotube based transparent immunosensor for detection of a prostate cancer biomarker osteopontin

“…The OPN concentration in prostate and normal patient sera was reported to be 653 AE 39 ng mL À1 and 439 AE 30 ng mL À1 , respectively [12]. Also, the average level of free OPN in plasma was 45 AE 20 ng mL À1 in normal samples and 127 AE 80 ng mL À1 in prostate cancer samples [13]. The RRCs for given OPN concentration were the smallest in a PBS medium and the largest in undiluted human serum, which can be attributed to non-specific binding of several other proteins in the serum.…”

“…OPN is a potential new biomarker of prostate cancer [12][13][14]. It is a secreted, 60-kDa phosphoprotein that cancer cells use to facilitate their expansion and can be expressed in a variety of tissues such as bones, brain, kidney, lung, and liver [15].…”

“…It is involved in almost all the steps of cancer development, and it is being investigated both as a new therapeutic target and as a potential biomarker for a diagnosis and prognosis of prostate cancer [14][15][16]. The measurements of free OPN, which is not bound to complement factor H, in plasma showed an increase with the stage of prostate cancer [13] although early detection with OPN measurements has not been fully established, requiring more studies [17]. It should also be noticed that OPN measurements are important for the prediction of prostate patient survival and for detection of other cancers.…”