DNA Integrity Assay: A Plasma-Based Screening Tool for the Detection of Prostate Cancer

Abstract

Purpose: The aim of this study was to evaluate the utility of the DNA integrity assay (DIA) as a plasma-based screening tool for the detection of prostate cancer. Experimental Design: Blood samples were collected from patients with biopsy-proven prostate cancer prior to prostatectomy (n = 123) and processed as two-spin plasma preparations. The three control groups included: males <40 years old with no history of cancer (group 1, n = 20); cancer-free postprostatectomy patients (group 2, n = 25), and patients with a negative prostate biopsy (group 3, n = 22). DNA in plasma preparations were isolated, hybrid-captured, and DNA fragments (200 bp, 1.3, 1.8, and 2.4 kb) were multiplexed in real-time PCR. A baseline cutoff was determined for individual fragment lengths to establish a DIA score for each patient sample. Results: Patients with prostate cancer (86 of 123; 69.9%) were determined to have a positive DIA score of z7. The DIA results from control groups 1, 2, and 3 showed specificities of 90%, 92%, and 68.2%, respectively. Of the patients with negative age-adjusted prostate-specific antigen (PSA) and prostate cancer, 19 of 30 (63%) had a positive DIA score. The area under the receiver operating characteristic curve for DIA was 0.788. Conclusion: While detecting 69.9 % of those with prostate cancer, DIA maintained an overall specificity of 68.2% to 92%, a range favorably comparable to that currently accepted for PSA (60-70%). The variability in specificity between control groups is likely explained by the established 19% to 30% detection of prostate cancer on subsequent biopsies associated with control group 3. DIA detected 63% of the prostate cancers undetected by currently accepted PSA ranges.

Circulating cell-free DNA in plasma of melanoma patients: Qualitative and quantitative considerations

“…In support to this hypothesis, recent studies demonstrated increased DNA length in plasma from patients with breast [5] and gynecologic cancers in comparison to healthy subjects [6]. Moreover, DNA characterized by higher integrity could be evidenced in cancer of the head and neck [7], prostate [8], kidney [9,10], esophagus [11], nasopharynx [12] and colon [13]. The test is based on the hypothesis that DNA fragments in plasma of cancer patients are longer than those detectable in healthy individuals.…”

Monitoring tumor-derived cell-free DNA in patients with solid tumors: Clinical perspectives and research opportunities

“…It was seen that the DNA integrity was higher in PCA patients than in controls [85]. Ellinger et al demonstrated that the DNA integrity was a predictor of PSA recurrence following radical prostatectomy and that the DNA integrity may allow to recognize PCA patients and benign prostate hyperplasia patients with a specificity of 81% and a sensitivity of 68% [77].…”

Genomic profiling of cell-free DNA in blood and bone marrow of prostate cancer patients

“…In this context, the detection and characterization of cell-free DNA in the peripheral blood from tumor patients have attracted great interest in biomedical research. Until now, only few studies have been conducted to explore the prognostic potential of cell-free DNA in prostate cancer (Chun et al 2006;Hanley et al 2006).…”