Serum Free Circulating DNA Is a Useful Biomarker to Distinguish Benign versus Malignant Prostate Disease

Abstract

Background: Free circulating DNA (fcDNA) has been shown to be elevated in serum of prostate cancer patients compared with benign controls. However, studies evaluating the role of fcDNA as a biomarker in a "representative" patient group who have undergone prostate cancer screening are lacking. Our study examined the use of serum fcDNA levels as a biomarker of prostate cancer in such a setting.Methods: The study included 252 men, with prostate-specific antigen (PSA) levels >4 ng/mL and/or abnormal digital rectal exam. fcDNA levels in serum before prostate biopsy were quantitated by real-time PCR amplification of the glutathione S-transferase, pi, gene.Results: Patients with PSA ≤ 10 ng/mL with fcDNA > 180 ng/mL were at increased risk for prostate cancer compared with those with fcDNA ≤180 ng/mL (odds ratio, 4.27; 95% confidence interval, 2.05-8.88; P < 0.001; area under the curve, 0.742). The multivariate model including age, race, PSA, fcDNA, and interaction between fcDNA and PSA yielded a high negative predictive value of 93.1% and increased specificity of 33.1% compared with negative predictive value of 73.3% and specificity of 6.7% in the model excluding fcDNA.Conclusions: Our results indicate that fcDNA may improve the specificity of prostate cancer screening. Impact: Our study shows that adding fcDNA to prostate cancer screening can reduce the number of unnecessary prostate biopsies. Cancer Epidemiol Biomarkers Prev; 19(8); 1984-91. ©2010 AACR.

Circulating cell-free DNA in serum as a biomarker of colorectal cancer

“…On the other hand, during necrosis, apoptosis, autophagy and mitochondrial catastrophe, the tumour cells release DNA fragments of different sizes, which leads to raised levels of circulating cell-free DNA with longer fragments in serum or plasma 21. These studies have shown the existence of elevated levels of circulating cell-free DNA, probably released from cancer cells into the plasma or serum, which occurs in several types of cancer, such as lung,13 14 22 23 renal,9 prostate,28 29 breast,16 19 21 26 27 and CRC 15 18 20 25…”

Clinical Relevance of Circulating Nucleic Acids in Blood of Prostate Cancer Patients

“…It was also reported, that patients with PSA of ≤10 ng/mL and cell-free DNA of > 180 ng/mL were at increased risk for prostate cancer compared with those with DNA of ≤180 ng/mL. Summing up, these findings show that cellfree DNA improved the specificity of prostate cancer screening and might, therefore, reduce the number of unnecessary prostate biopsies (Gordian et al, 2010). Ellinger et al designed a study to evaluate the apoptosis index which expresses the ratio of prostaglandin-endoperoxide synthase 2 (PTGS2) to Reprimo DNA fragments.…”

Structural and molecular biology of PSP94 Its significance in prostate pathophysiology

“…A recent nested case-control study, carried out in multiple populations, reported significantly high sPSA levels in patients with PCa as compared to healthy men (69). Further, the sPSA levels were also found to be highest in PCa than in healthy men (72) or BPH patients (176), irrespective of the racial diversity. The combined results of three separate recent Indian studies also show the sPSA levels to be highest in PCa, intermediate in BPH and lowest in healthy conditions (50,177,178).…”