This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Current techniques for the screening and risk assessment of prostate cancer, as a prerequisite to surgical biopsy procedures, are based upon the measurement of either individual serum biomarkers, or expression of individual genes in circulating malignant cells. These techniques possess a number of limitations, including lack of specificity and accuracy in the diagnosis and, also a lack of prognostic information. This ultimately yields high numbers of false positive diagnoses, and consequently unnecessarily large numbers of surgical biopsies. There is growing evidence that individuals with prostate cancer and other forms of malignant disease, exhibit immune responses that can be detected at the level of altered gene expression in leukocytes circulating in peripheral blood. Quantitation of the mRNA transcripts in leukocytes of a number of individual genes has demonstrated associations between gene expression levels and the presence of a tumor. It has been shown that serum levels of individual proteins exhibit a degree of correlation with differential gene expression in leukocytes, and provides some information on tumor stage. Additionally, we have initiated a pilot study to examine gene expression levels in African-American men with prostate cancer, and have shown expression difference for multiple genes, compared to healthy controls of multiple genes. Hypothesis: These observations form the basis of the hypothesis and experimental design of this proposed study. The use of microarray technology will allow us to measure simultaneously the expression levels of up to 14,000 genes transcribed in circulating leukocytes derived from the blood of prostate cancer patients and control individuals. With this technology, we propose to investigate the hypothesis that individuals suffering from prostate cancer exhibit a conserved pattern, or signature, of gene expression levels in their peripheral blood leukocytes, which is distinct from the corresponding pattern of expression in leukocytes from control subjects. We will test the further hypothesis that cancer patients with prostate tumors at different histological grades, will yield distinct expression signatures that reflect the biological stage and aggressiveness of the tumor, and that can thus be employed to differentiate among tumors at different pathological stages.
The Specific aims of this entire proposal are to:
Specific Aim One : a) Collect Blood Leukocytes from 40 Prostate Cancer Patients and 20 Healthy Control Subjects Over the Two Year Period of This Project. b) Employ Affymetrix GeneChip Microarray Technology to Measure Global Gene Expression in the Leukocyte Samples. c) Employ Data Analysis Algorithms to Establish Leukocyte Multigene Expression Signatures that Can Distinguish Between Prostate Cancer Patients and Control Subjects.
Specific Aim Two : Utilize the Expression Data Generated Under Specific Aim One, to Permit Classification of Prostate Cancer Patients into Groups Corresponding to Specific Stages of Prostate Tumor Progression. Ultimate Goal of this Proposal. The ultimate goal of the research proposed here is to develop a novel technique that does not require invasive surgery, yet provides an accurate diagnosis of prostate cancer, and also provides detailed prognostic information on the stage and biological aggressiveness of the tumor. The success of this project would yield a much needed, non-invasive tool for stage-specific diagnosis of prostate cancer of the disease, and thus serve as an important pre-screen to identify men with prostate tumors.
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