Recent evidence has shown elevated levels of cell-free plasma DNA in cancer patients. The aim of the present study was to quantify and compare the levels of cell-free plasma DNA in patients with prostate cancer, prostatic intraepithelial neoplasia (PIN), and benign prostatic hypertrophy (BPH) to examine if it offered a useful diagnostic test. Blood samples were obtained from 37 patients attending a clinic for prostate biopsies. Samples were taken prior to biopsy, within 1 hour of the biopsy, and then 2 weeks later. DNA was extracted using a QIAamp blood kit (Qiagen) and plasma DNA measured, in genome equivalents/milliliter plasma (GE/mL), using real-time quantitative PCR for the beta-globin gene. Prior to biopsy, plasma DNA concentration in BPH patients was 936 GE/mL (median; range: 633-2074 GE/mL), while cancer and PIN patients had significantly higher levels of DNA at 1734 GE/mL (median; range: 351-3131 GE/mL; P = 0.01) and 1780 GE/mL (median; range: 1514-2732 GE/mL; P = 0.04), respectively. Comparison of plasma DNA concentration before and after biopsy showed that 60 minutes after biopsy values were significantly higher in both BPH (1494 GE/mL; range: 613-2522 GE/mL; P = 0.029) and cancer (2758; range: 1498-5226 GE/mL; P = 0.007) patients. ROC analysis of the data indicated a sensitivity of 85% and a specificity of 73% when DNA concentration of 1000 GE/mL was taken as an indicator of malignancy or PIN. The data suggest that quantification of cell-free plasma DNA may have an important diagnostic role in distinguishing benign and malignant prostate disease.
used for decision tree building. A blinded test set consisting of 20 controls and 320 CaP patients was used to challenge the algorithms. Additional control specimens are being collected for further analysis.RESULTS: A decision tree algorithm consisting of 4 discriminatory peaks with mass designations of 4067Da and 12617Da on the WCX2 array and 7782Da and 9306Da on the IMAC3-Cu array was generated by Biomarker Patterns Software. The algorithm correctly identified 255 of the 320 CaP patients and 17 of the 20 controls in the test set giving a sensitivity of 80% and specificity of 85% on validation.CONCLUSIONS: Using a larger cohort of CaP patients and streamlined robotic processing of specimens, serum proteomic profiling using SELDI-TOF in a follow-up study continues to show promising potential for CaP detection with high sensitivity and specificity. Further evaluations/development of this new technology is underway including additional specimens and new algorithms for the analysis of the same data set Source of Funding: U.S. Department of Defense and the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.