This proposal will define a molecular classification schema for organ-confined prostate cancer. The schema will be based on patterns of gene expression and DNA methylation found within prostate tumors and the surrounding stroma.
The aim of the project is to create a method for classifying such tumors based on tumor biology rather than simply on histology. The development of a classification schema based on molecular profiles would improve our ability to treat and manage organ-confined prostate cancer. Four complementary approaches to the generation of molecular profiles will be used. Gene expression molecular profiles will be generated using 1) Affymetrix Gene Chip technology and 2) RNA arbitrarily primed (RAP-PCR) based cDNA array analysis. DNA methylation molecular profiles of will be generated using 1) methylation-sensitive array analysis and 2) restriction landmark genomic scanning (RLGS). The utility and complementarity of each approach in relation to the others will be evaluated. Prospective clinical data will be collected to allow for the correlation of each molecular profile with important tumor characteristics. With the completion of this project we expect that we will have: Defined a molecular profile for organ-confined prostate cancer that will supplant the standard pathologic diagnosis and staging of these tumors. Defined additional profiles that correlate with important clinical characteristics in these patients. Such characteristics should include both important pathologic parameters (i.e. Gleason score, PSA levels, stage), and clinical outcome (likelihood of metastatic disease, likelihood of hormonal, radiation or chemotherapy response, time to progression and survival). Discovering molecular profiles within prostate tumors that prognosticate for patient outcome will greatly improve the quality of life for these patients.
|Wang, Yipeng; Xia, Xiao-Qin; Jia, Zhenyu et al. (2010) In silico estimates of tissue components in surgical samples based on expression profiling data. Cancer Res 70:6448-55|
|Baron, V; Adamson, E D; Calogero, A et al. (2006) The transcription factor Egr1 is a direct regulator of multiple tumor suppressors including TGFbeta1, PTEN, p53, and fibronectin. Cancer Gene Ther 13:115-24|
|Spence, Jean; Duggan, Brendan M; Eckhardt, Colleen et al. (2006) Messenger RNAs under differential translational control in Ki-ras-transformed cells. Mol Cancer Res 4:47-60|
|Wang, Yipeng; Yu, Qiuju; Cho, Ann H et al. (2005) Survey of differentially methylated promoters in prostate cancer cell lines. Neoplasia 7:748-60|
|Wang, Yipeng; Hayakawa, Jun; Long, Fred et al. (2005) ""Promoter array"" studies identify cohorts of genes directly regulated by methylation, copy number change, or transcription factor binding in human cancer cells. Ann N Y Acad Sci 1058:162-85|
|Hayakawa, Jun; Mittal, Shalu; Wang, Yipeng et al. (2004) Identification of promoters bound by c-Jun/ATF2 during rapid large-scale gene activation following genotoxic stress. Mol Cell 16:521-35|
|Stuart, Robert O; Wachsman, William; Berry, Charles C et al. (2004) In silico dissection of cell-type-associated patterns of gene expression in prostate cancer. Proc Natl Acad Sci U S A 101:615-20|
|Sloan, Derek D; Nicholson, Ben; Urquidi, Virginia et al. (2004) Detection of differentially expressed genes in an isogenic breast metastasis model using RNA arbitrarily primed-polymerase chain reaction coupled with array hybridization (RAP-array). Am J Pathol 164:315-23|
|Adamson, Eileen; de Belle, Ian; Mittal, Shalu et al. (2003) Egr1 signaling in prostate cancer. Cancer Biol Ther 2:617-22|
|Yang, Yong-Min; Bost, Frederic; Charbono, Wilfried et al. (2003) C-Jun NH(2)-terminal kinase mediates proliferation and tumor growth of human prostate carcinoma. Clin Cancer Res 9:391-401|
Showing the most recent 10 out of 14 publications