Molecular and Clinical Predictors of Aggressive Prostate Cancer
Final rept. 1 Sep 2005-31 Aug 2008
BRIGHAM AND WOMEN'S HOSPITAL BOSTON MA
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While prostate cancer is an important cause of cancer mortality, most men diagnosed with early prostate cancer experience an indolent course. We evaluated molecular and clinical predictors to distinguish lethal and indolent prostate cancer. In a related project, we tested the predictive value of a previously identified multigene tumor signature, a 12-gene model. Risk classification based on the 12-gene model predicted development of lethal disease 20 years hence. The best discrimination came from combining data from the 12-gene markers and clinical data, which perfectly classified the lowest risk stratum where no one died of cancer and provided greater discriminatory ability AUC 0.78 than the clinical model alone AUC 0.71, p0.04. We tested the top 5-genes from the model, and additional tumor markers, within a prostatectomy cohort of 950 men from the Physicians Health Study and Health Professionals Follow-up Study. We constructed high-density tumor tissue microarrays, and undertook immunohistochemistry to characterize protein expression. We abstracted clinical data from medical records and pathology reports. We undertook statistical analyses and model building to test the discriminatory ability of the gene markers and clinical data, with the ultimate goal to provide prognostication of lethal and indolent prostate cancer.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research