Plasma Cell-free DNA and Its DNA Integrity As Biomarker to Distinguish Prostate Cancer from Benign Prostatic Hyperplasia in Patients with Increased Serum Prostate-specific Antigen

Overview

Journal Int Urol Nephrol

Publisher Springer

Specialty Nephrology

Date 2013 Jun 20

PMID 23779229

Citations 32

Authors

Jiang Feng

Feng Gang

Xiao Li

Tang Jin

Huang Houbao

Cao Yu

Li Guorong

Affiliations

Soon will be listed here.

Abstract

Objectives: To investigate whether plasma cell-free DNA (cfDNA) or its integrity could differentiate prostate cancer from benign prostate hyperplasia (BPH) in patients with serum prostate-specific antigen (PSA) ≥ 4 ng/ml.

Methods: Ninety-six patients with prostate cancer and 112 patients with BPH were enrolled. cfDNA levels in plasma before prostate biopsy were quantified by real-time PCR amplification of ALU gene (product size of 115 bp), and quantitative ratio of ALU (247 bp) to ALU (115 bp) reflected the integrity of cfDNA.

Results: In patients with serum PSA ≥ 4 ng/ml, there were significant differences in plasma cfDNA or its integrity between the patients with prostate cancer (19.74 ± 4.43, 0.34 ± 0.05) and patients with BPH (7.36 ± 1.58, 0.19 ± 0.03; P < 0.001, P < 0.001). Prostate cancer could be differentiated with a sensitivity of 73.2 % and a specificity of 72.7 % by cfDNA (AUC = 0.864). The integrity of cfDNA had a sensitivity of 81.7 % and a specificity of 78.8 % for the distinguishing prostate cancer from BPH (AUC = 0.910).

Conclusions: cfDNA and its integrity could be applied to differentiate prostate cancer from BPH in patients with serum PSA ≥ 4 ng/ml.

Citing Articles

Circulating Cell-Free DNA Integrity for Breast and Prostate Cancer: What Is the Landscape for Clinical Management of the Most Common Cancers in Women and Men?.

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Liquid Biopsies Based on Cell-Free DNA Integrity as a Biomarker for Cancer Diagnosis: A Meta-Analysis.

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Targeted Sequencing of Human Satellite 2 Repeat Sequences in Plasma cfDNA Reveals Potential Breast Cancer Biomarkers.

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How to Integrate Prostate Cancer Biomarkers in Urology Clinical Practice: An Update.

Baston C, Preda A, Iordache A, Olaru V, Surcel C, Sinescu I Cancers (Basel). 2024; 16(2).

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Combinations of plasma cfDNA concentration, integrity and tumor markers are promising biomarkers for early diagnosis of non-small cell lung cancer.

Ren S, Zeng G, Yi Y, Liu L, Tu H, Chai T Heliyon. 2023; 9(10):e20851.

PMID: 37860559 PMC: 10582504. DOI: 10.1016/j.heliyon.2023.e20851.

References

Gordian E, Ramachandran K, Reis I, Manoharan M, Soloway M, Singal R . Serum free circulating DNA is a useful biomarker to distinguish benign versus malignant prostate disease. Cancer Epidemiol Biomarkers Prev. 2010; 19(8):1984-91. DOI: 10.1158/1055-9965.EPI-10-0287. View

Papadopoulou E, Davilas E, Sotiriou V, Koliopanos A, Aggelakis F, Dardoufas K . Cell-free DNA and RNA in plasma as a new molecular marker for prostate cancer. Oncol Res. 2004; 14(9):439-45. DOI: 10.3727/0965040041791473. View

Umetani N, Giuliano A, Hiramatsu S, Amersi F, Nakagawa T, Martino S . Prediction of breast tumor progression by integrity of free circulating DNA in serum. J Clin Oncol. 2006; 24(26):4270-6. DOI: 10.1200/JCO.2006.05.9493. View

Altimari A, Grigioni A, Benedettini E, Gabusi E, Schiavina R, Martinelli A . Diagnostic role of circulating free plasma DNA detection in patients with localized prostate cancer. Am J Clin Pathol. 2008; 129(5):756-62. DOI: 10.1309/DBPX1MFNDDJBW1FL. View

Boddy J, Gal S, Malone P, Harris A, Wainscoat J . Prospective study of quantitation of plasma DNA levels in the diagnosis of malignant versus benign prostate disease. Clin Cancer Res. 2005; 11(4):1394-9. DOI: 10.1158/1078-0432.CCR-04-1237. View

Strope S, Andriole G . Prostate cancer screening: current status and future perspectives. Nat Rev Urol. 2010; 7(9):487-93. DOI: 10.1038/nrurol.2010.120. View

Wang B, Huang H, Chen Y, Bristow R, Kassauei K, Cheng C . Increased plasma DNA integrity in cancer patients. Cancer Res. 2003; 63(14):3966-8. View

Gui-Zhong L, Libo M, Guanglin H, Jianwei W . The correlation of extent and grade of inflammation with serum PSA levels in patients with IV prostatitis. Int Urol Nephrol. 2010; 43(2):295-301. DOI: 10.1007/s11255-010-9825-5. View

Gang F, Guorong L, An Z, Anne G, Christian G, Jacques T . Prediction of clear cell renal cell carcinoma by integrity of cell-free DNA in serum. Urology. 2009; 75(2):262-5. DOI: 10.1016/j.urology.2009.06.048. View

10.

Heijnsdijk E, der Kinderen A, Wever E, Draisma G, Roobol M, de Koning H . Overdetection, overtreatment and costs in prostate-specific antigen screening for prostate cancer. Br J Cancer. 2009; 101(11):1833-8. PMC: 2788248. DOI: 10.1038/sj.bjc.6605422. View

11.

Kumar S, Guleria R, Singh V, Bharti A, Mohan A, Das B . Efficacy of circulating plasma DNA as a diagnostic tool for advanced non-small cell lung cancer and its predictive utility for survival and response to chemotherapy. Lung Cancer. 2010; 70(2):211-7. DOI: 10.1016/j.lungcan.2010.01.021. View

12.

Heidenreich A, Aus G, Bolla M, Joniau S, Matveev V, Schmid H . EAU guidelines on prostate cancer. Eur Urol. 2007; 53(1):68-80. DOI: 10.1016/j.eururo.2007.09.002. View

13.

Ellinger J, Wittkamp V, Albers P, Perabo F, Mueller S, von Ruecker A . Cell-free circulating DNA: diagnostic value in patients with testicular germ cell cancer. J Urol. 2008; 181(1):363-71. DOI: 10.1016/j.juro.2008.08.118. View

14.

Schwarzenbach H, Hoon D, Pantel K . Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer. 2011; 11(6):426-37. DOI: 10.1038/nrc3066. View

15.

Schwarzenbach H, Alix-Panabieres C, Muller I, Letang N, Vendrell J, Rebillard X . Cell-free tumor DNA in blood plasma as a marker for circulating tumor cells in prostate cancer. Clin Cancer Res. 2009; 15(3):1032-8. DOI: 10.1158/1078-0432.CCR-08-1910. View

16.

Hanley R, Rieger-Christ K, Canes D, Emara N, Shuber A, Boynton K . DNA integrity assay: a plasma-based screening tool for the detection of prostate cancer. Clin Cancer Res. 2006; 12(15):4569-74. DOI: 10.1158/1078-0432.CCR-06-0130. View

17.

Porcaro A, Migliorini F, Romano M, Petrozziello A, Zecchini Antoniolli S, Rubilotta E . Investigative clinical study on prostate cancer: on the role of the pretreatment total PSA to free testosterone ratio in selecting different biology groups of prostate cancer patients. Int Urol Nephrol. 2009; 42(3):673-81. DOI: 10.1007/s11255-009-9669-z. View

18.

Wu T, Zhang D, Chia J, Sun C, Wu J . Cell-free DNA: measurement in various carcinomas and establishment of normal reference range. Clin Chim Acta. 2002; 321(1-2):77-87. DOI: 10.1016/s0009-8981(02)00091-8. View

19.

Strittmatter F, Stieber P, Nagel D, Fullhase C, Walther S, Stief C . Detection of prostate cancer with complexed PSA and complexed/total PSA ratio - is there any advantage?. Eur J Med Res. 2011; 16(10):445-50. PMC: 3400975. DOI: 10.1186/2047-783x-16-10-445. View

20.

Jemal A, Siegel R, Xu J, Ward E . Cancer statistics, 2010. CA Cancer J Clin. 2010; 60(5):277-300. DOI: 10.3322/caac.20073. View