International Urology and Nephrology

, Volume 45, Issue 4, pp 1023–1028 | Cite as

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

  • Jiang Feng
  • Feng Gang
  • Xiao Li
  • Tang Jin
  • Huang Houbao
  • Cao Yu
  • Li Guorong
Urology - Original Paper



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.


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.


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).


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


Plasma cell-free DNA Integrity of cell-free DNA Prostate cancer Benign prostate hyperplasia 



This research was supported by Yijishan Hospital of Wannan Medical College (WK2011F26 and YR201112).

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60:277–300PubMedCrossRefGoogle Scholar
  2. 2.
    Strope SA, Andriole GL (2010) Prostate cancer screening: current status and future perspectives. Nat Rev Urol 7:487–493PubMedCrossRefGoogle Scholar
  3. 3.
    Porcaro AB, Migliorini F, Romano M et al (2010) 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 42:673–681PubMedCrossRefGoogle Scholar
  4. 4.
    Heijnsdijk EA, der Kinderen A, Wever EM et al (2009) Overdetection, overtreatment and costs in prostate-specific antigen screening for prostate cancer. Br J Cancer 101:1833–1838PubMedCrossRefGoogle Scholar
  5. 5.
    Wang BG, Huang HY, Chen YC et al (2003) Increased plasm DNA integrity in cancer patients. Cancer Res 63:3966–3968PubMedGoogle Scholar
  6. 6.
    Schwarzenbach H, Hoon DS, Pantel K (2011) Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer 11:426–437PubMedCrossRefGoogle Scholar
  7. 7.
    Schwarzenbach H, Alix-Panabières C, Müller I et al (2009) Cell-free tumor DNA in blood plasma as a marker for circulating tumor cells in prostate cancer. Clin Cancer Res 15:1032–1038PubMedCrossRefGoogle Scholar
  8. 8.
    Umetani N, Giuliano AE, Hiramatsu SH et al (2006) Prediction of breast tumor progression by integrity of free circulating DNA in serum. J Clin Oncol 24:4270–4276PubMedCrossRefGoogle Scholar
  9. 9.
    Gui-Zhong L, Libo M, Guanglin H et al (2011) The correlation of extent and grade of inflammation with serum PSA levels in patients with IV prostatitis. Int Urol Nephrol 43:295–301PubMedCrossRefGoogle Scholar
  10. 10.
    Heidenreich A, Aus G, Bolla M et al (2008) Eau guidelines on prostate cancer. Eur Urol 53:68–80PubMedCrossRefGoogle Scholar
  11. 11.
    Strittmatter F, Stieber P, Nagel D et al (2011) Detection of prostate cancer with complexed PSA and complexed/total PSA ratio—is there any advantage? Eur J Med Res 16:445–450PubMedCrossRefGoogle Scholar
  12. 12.
    Ellinger J, Wittkamp V, Albers P et al (2009) Cell-free circulating DNA: diagnostic value in patients with testicular germ cell cancer. J Urol 181:363–371PubMedCrossRefGoogle Scholar
  13. 13.
    Kumar S, Guleria R, Singh V et al (2010) 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 70:211–217PubMedCrossRefGoogle Scholar
  14. 14.
    Gang F, Guorong L, An Z et al (2010) Prediction of clear cell renal cell carcinoma by integrity of cell-free DNA in serum. Urology 75:262–265PubMedCrossRefGoogle Scholar
  15. 15.
    Wu TL, Zhang D, Chia JH et al (2002) Cell-free DNA: measurement in various carcinomas and establishment of normal reference range. Clin Chim Acta 321:77–87PubMedCrossRefGoogle Scholar
  16. 16.
    Papadopoulou E, Davilas E, Sotiriou V et al (2004) Cell-free DNA in plasma as a new molecular marker for prostate cancer. Oncol Res 14:439–445PubMedGoogle Scholar
  17. 17.
    Altimari A, Grigioni AD, Benedettini E et al (2008) Diagnostic role of circulating free plasma DNA detection in patients with localized prostate cancer. Am J Clin Pathol 129:756–762PubMedCrossRefGoogle Scholar
  18. 18.
    Boddy JL, Gal S, Malone PR et al (2005) Prospective study of quantitation of plasma DNA levels in the diagnosis of malignant versus benign prostate disease. Clin Cancer Res 11:1394–1399PubMedCrossRefGoogle Scholar
  19. 19.
    Gordian E, Ramachandran K, Reis IM et al (2010) Serum free circulating DNA is a useful biomarker to distinguish benign versus malignant prostate disease. Cancer Epidemiol Biomarkers Prev 19:1984–1991PubMedCrossRefGoogle Scholar
  20. 20.
    Hanley R, Rieger-Christ KM, Canes D et al (2006) DNA integrity assay: a plasma-based screening tool for the detection of prostate cancer. Clin Cancer Res 12:4569–4574PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Jiang Feng
    • 1
  • Feng Gang
    • 3
  • Xiao Li
    • 4
  • Tang Jin
    • 5
  • Huang Houbao
    • 2
  • Cao Yu
    • 6
  • Li Guorong
    • 7
  1. 1.Department of UltrasoundYijishan Hospital of Wannan Medical CollegeWuhuChina
  2. 2.Department of UrologyYijishan Hospital of Wannan Medical CollegeWuhuChina
  3. 3.Clinical Genetics LaboratoryYijishan Hospital of Wannan Medical CollegeWuhuChina
  4. 4.Department of UltrasoundThird Xiangya Hospital of Central-south UniversityChangshaChina
  5. 5.Department of UrologyThird Xiangya Hospital of Central-south UniversityChangshaChina
  6. 6.Department of CardiologyThird Xiangya Hospital of Central-south UniversityChangshaChina
  7. 7.Department of Urology, North HospitalCHU of Saint-EtienneSaint-ÉtienneFrance

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