Serum Genetic Markers as Surrogates of Prostate Cancer Progression; Final rept. 1 Apr 2003-31 Mar 2008

摘要

As proposed, we have successfully established assays to detect free tumor-related DNA marker(s) in serum of prostate cancer (PCa) patients and studied the potential use of the biomarker detection as surrogate genetic markers in monitoring PCa patients. Despite slight delay in the beginning, the program has moved expediently over the years from assay development and optimization to subject sample accrual and assessment. DNA markers involving allelic instability (Al; 6 markers) and methylation of genes (3 markers) with high specificity and sensitivity were screened and established. Of the 83 AJCC stage I-IV PCa patients studied, the proportion of patients demonstrating Al for greater or equal to 1 marker was 47% (38/81 patients). Methylation biomarkers were detected in 24/83 (28%) patients. By combining two DNA assays, the number of PCa patients positive for greater or equal to 1 methylated or Al marker increased to 52/83 (63%). The combined assays detected PCa in 15 of 24 (63%) patients with normal PSA levels. The combination of the DNA biomarker assays detected the presence of PCa regardless of AJCC stage of PSA level. The results obtained through this award demonstrate that tumor-related DNA marker serum assay may be used, independent of AJCC stage or PSA level, in identifying and monitoring patients with PCa.