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Chemokine Prostate Cancer Biomarkers

Macoska, JillUniversity of Massachusetts, Boston

No involved investigator sites defined.

CXCL5 and CXCL12
Prostate and Urologic Cancers Research Group

STUDY DESIGN 1. The need for pre-validation studies. Preliminary data from our laboratory demonstrates a potential utility for CXCL5 and CXCL12 as biomarkers to distinguish between patients at high-risk versus low-risk for harboring prostate malignancies. However, this pilot and feasibility study utilized a very small sample size of 51 patients, which limited the ability of this study to adequately assess certain technical aspects of the ELISA technique and statistical aspects of we propose studies designed assess the robustness (Specific Aim 1) and predictive value (Specific Aim 2) of these markers in a larger study population. 2. ELISA Assays. Serum, plasma, or urine chemokine levels are assessed using 50 ul frozen specimen per sandwich ELISA in duplicate using the appropriate commercially-available capture antibodies, detection antibodies, and standard ELISA reagents (R&D; Systems), as we have described previously (15, 17, 18). Measures within each patient group are regarded as biological replicates and permit statistical comparisons between groups. For all ELISAs, a standard curve is generated with the provided standards and utilized to calculate the quantity of chemokine in the sample tested. These assays provide measures of protein concentration with excellent reproducibility, with replicate measures characterized by standard deviations from the mean on the order of <3%.

SPECIFIC AIMS/DELIVERABLES. In order to test this hypothesis, we will accomplish two Specific Aims: Specific Aim 1. Assess the robustness of serum, plasma, or urine measures of CXCL5 and CXCL12. Specific Aim 2. Determine whether serum, plasma, or urine levels of CXCL5 and CXCL12 provide sufficient predictive value for prostate cancer among men with low (<10ng/ml) total serum PSA.
The results of these assays will determine whether statistically significant associations between disease status in the prostate (no disease, BPH, PCa with or without concomitant BPH) and serum, plasma, or urine protein levels for CXCL5 and/or CXCL12 are observed among patients with low but detectable serum PSA. If so, then ROC analyses will determine whether the sensitivity and specificity of these protein levels to ‘predict’ disease status are superior to those of PSA or other similarly evaluated biomarkers as reported in the literature. If so, a larger, multiinstitutional study to validate these findings across a broader patient population will be pursued through collaborative efforts within the NCI-sponsored Early Detection Research Network (EDRN) to validate these findings. Conversely, if no statistically significant associations between disease status in the prostate and serum, plasma, or urine protein levels for CXCL5 and/or CXCL12 are observed, then we will conclude that these proteins do not comprise suitable biomarkers for disease status in the prostate, and that further studies are not warranted.
Aim 1 is completed, Aim 2 is in prcess

There are currently no biomarkers annotated for this protocol.

No datasets are currently associated with this protocol.

New Funding Opportunity: Biomarker Development Laboratories for the Early Detection Network: Applications Due May 23

Update: Pre-application webinar information now available.

The National Cancer Institute's Division of Cancer Prevention has released a new funding opportunity to solicit organ-specific applications for Biomarker Developmental Laboratories (BDLs), one of the four scientific units of the recently funded Early Detection Research Network (EDRN). The EDRN is a national infrastructure funded to discover, develop, and validate biomarkers for risk assessment, detection, and molecular diagnosis and prognosis of early cancer. BDLs are responsible for the discovery, development, characterization, and testing of new, or the refinement of existing, biomarkers and biomarker assays for risk assessment, detection, and molecular diagnosis and prognosis of cancers.

The existing BDLs are primarily focused on ovary and gastrointestinal cancers. The proposed BDLs (to be supported under this funding opportunity) should be focused on one or more of the following cancers: breast, prostate and other genitourinary organs, or lung. In addition, cancers with rapidly rising incidence rates, e.g., endometrial, hepatocellular, kidney, thyroid, oropharyngeal cancers, and/or cancers with unique etiology, e.g., mesothelioma, will be considered.

The newly funded units of the Early Detection Research Network will be announced later in April. Successful applicants have already been notified. Those researchers who were not successful during the last round of applications are encouraged to apply to this opportunity.