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A New Biomarker for Hepatocellular Damage: Plasma Cell-Free DNA

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DOI: 10.4236/aa.2012.24023    3,295 Downloads   7,445 Views   Citations


Background: Accumulating evidence has suggested that cell-free DNA (cf-DNA) enters the circulation following cell apoptosis or necrosis. An increased level of cf-DNA fragments has been found in the blood of mice with drug-induced liver damage. We sought to determine the role of cf-DNA in hepatocellular damage. Methods: Plasma samples were collected from 204 patients with hepatitis. The patients were divided into three groups according to liver pathologic characteristics: with chronic hepatitis (CH) and compensated liver cirrhosis (LC) (the group 1); with decompensated liver cirrhosis (DLC) (the group 2); with liver failure (LF), acute hepatitis (AH) and hepatocellular carcinoma (HCC) (the group 3). The cf-DNA was extracted with the phenol/chloroform/isoamyl alcohol (PCI) method and the plasma cf-DNA was quantified using real-time polymerase chain reaction (rt-PCR) for β-globin. The cf-DNA copies were converted to log2 values for comparison. Results: Cf-DNA was detected in all the 3 groups. The group 3 had a significantly higher cf-DNA level than the other two groups (17.70 ± 1.79, P = 0.002). The level of plasma cf-DNA was correlated with the baseline aniline transaminase (ALT) and aspertate transaminase (AST) activities (P < 0.005). The cf-DNA concentration in patients with cirrhosis was correlated with the model of end-stage liver disease-Na (MELD-Na) score and the ALT and AST activities. Correlation of the cf-DNA level with laboratory parameters, such as bilirubin and international normalized ratio (INR), were found in patients with high cf-DNA levels (cf-DNA > 19.5), or with severe hepatocellular damage (ALT > 500 U/L). Conclusion: Plasma cell-free DNA may be a new promising, independent, non-invasive biomarker for hepatocellular damage.

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The authors declare no conflicts of interest.

Cite this paper

Yan, Z. , He, Y. , Li, Q. , Cui, M. , Wang, K. , Chen, T. , Liu, H. & Zhao, Y. (2012). A New Biomarker for Hepatocellular Damage: Plasma Cell-Free DNA. Advances in Anthropology, 2, 214-220. doi: 10.4236/aa.2012.24023.


[1] Anker, P., Stroun, M., & Maurice, P. A. (1975). Spontaneous release of DNA by human blood lymphocytes as shown in an in vitro system. Cancer Research, 35, 2375-2382.
[2] Botezatu, I., Serdyuk, O., Potapova, G., Shelepov, V., Alechina, R., Molyaka, Y. et al. (2000). Genetic analysis of DNA excreted in urine: A new approach for detecting specific genomic DNA sequences from cells dying in an organism. Clinical Chemistry, 46, 1078-1084.
[3] Dufour, D. R., Lott, J. A., Nolte, F. S., Gretch, D. R., Koff, R. S., & Seeff, L. B. (2000). Diagnosis and monitoring of hepatic injury. II. Recommendations for use of laboratory tests in screening, diagnosis, and monitoring. Clinical Chemistry, 46, 2050-2068.
[4] Emlen, W., & Mannik, M. (1978). Kinetics and mechanisms for removal of circulating single-stranded DNA in mice. Journal of Experimental Medicine, 147, 684-699. doi:10.1084/jem.147.3.684
[5] Fong, S. L., Zhang, J. T., Lim, C. K., Eu, K. W., & Liu, Y. (2009). Comparison of 7 methods for extracting cell-free DNA from serum samples of colorectal cancer patients. Clinical Chemistry, 55, 587589. doi:10.1373/clinchem.2008.110122
[6] Holdenrieder, S., Eichhorn, P., Beuers, U., Samtleben, W., Schoenermarck, U., Zachoval, R. et al. (2006). Nucleosomal DNA fragments in autoimmune diseases. Annals of the New York Academy of Sciences, 1075, 318-327. doi:10.1196/annals.1368.043
[7] Hsu, C. Y., Lin, H. C., Huang, Y. H., Su, C. W., Lee, F. Y., Huo, T. I. et al. (2010). Comparison of the model for end-stage liver disease (MELD), MELD-Na and MELDNa for outcome prediction in patients with acute decompensated hepatitis. Digestive and Liver Disease, 42, 137-142. doi:10.1016/j.dld.2009.06.004
[8] Jahr, S., Hentze, H., Englisch, S., Hardt, D., Fackelmayer, F. O., Hesch, R. D., et al. (2001). DNA fragments in the blood plasma of cancer patients: Quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Research, 61, 1659-1665.
[9] Jung, M., Klotzek, S., Lewandowski, M., Fleischhacker, M., & Jung K. (2003). Changes in concentration of DNA in serum and plasma during storage of blood samples. Clinical Chemistry, 49, 1028-1029. doi:10.1373/49.6.1028
[10] Kamat, A. A., Baldwin, M., Urbauer, D., Dang, D., Han, L. Y., Godwin, A. et al. (2010). Plasma cell-free DNA in ovarian cancer: An independent prognostic biomarker. Cancer, 116, 1918-1925. doi:10.1002/cncr.24997
[11] Kamath, P. S., & Kim, W. R. (2007). The model for end-stage liver disease (MELD). Hepatology, 45, 797-805. doi:10.1002/hep.21563
[12] Lam, N. Y., Rainer, T. H., Chan, L. Y., Joynt, G. M., & Lo, Y. M. (2003). Time course of early and late changes in plasma DNA in trauma patients. Clinical Chemistry, 49, 1286-1291. doi:10.1373/49.8.1286
[13] Lam, N. Y., Rainer, T. H., Chiu, R. W., & Lo, Y. M. (2004). EDTA is a better anticoagulant than heparin or citrate for delayed blood processing for plasma DNA analysis. Clinical Chemistry, 50, 256-257. doi:10.1373/clinchem.2003.026013
[14] Lau, T. W., Leung, T. N., Chan, L. Y., Lau, T. K., Chan, K. C., Tam, W. H. et al. (2002). Fetal DNA clearance from maternal plasma is impaired in preeclampsia. Clinical Chemistry, 48, 2141-2146.
[15] Lee, T. H., Montalvo, L., Chrebtow, V., & Busch, M. P. (2001). Quantitation of genomic DNA in plasma and serum samples: Higher concentrations of genomic DNA found in serum than in plasma. Transfusion, 41, 276-282. doi:10.1046/j.1537-2995.2001.41020276.x
[16] Lo, Y. M., Zhang, J., Leung, T. N., Lau, T. K., Chang, A. M., & Hjelm, N. M. (1999). Rapid clearance of fetal DNA from maternal plasma. The American journal of Human Genetics, 64, 218-224. doi:10.1086/302205
[17] Lui, Y. Y., Chik, K. W., Chiu, R.W., Ho, C. Y., Lam, C. W., & Lo, Y. M. (2002). Predominant hematopoietic origin of cell-free DNA in plasma and serum after sex-mismatched bone marrow transplantation. Clinical Chemistry, 48, 421-427.
[18] Pratt, D. S., &Kaplan, M. M. (2007). Laboratory tests. In E. R. Schiff, (Ed.), Schiff’s diseases of the liver (10th ed., pp. 19-54). Hoboken, NJ: Wiley-Blackwell.
[19] Roth, G. A., Lubsczyk, B. A., Pilz, J., Faybik, P., Hetz, H., & Krenn, C. G. (2009). Nucleosome serum levels in acute hepatic failure and MARS treatment. Transplant Proceedings, 41, 4207-4210. doi:10.1016/j.transproceed.2009.08.073
[20] Tokuhisa, Y., Iizuka, N., Sakaida, I., Moribe, T., Fujita, N., Miura, T. et al. (2007). Circulating cell-free DNA as a predictive marker for distant metastasis of hepatitis C virus-related hepatocellular carcinoma. British Journal of Cancer, 97, 1399-1403. doi:10.1038/sj.bjc.6604034
[21] van der Vaart, M., & Pretorius, P. J. (2007). The origin of circulating free DNA. Clinical Chemistry, 53, 2215. doi:10.1373/clinchem.2007.092734
[22] World Health Organization (2003). The world health report 2003— Shaping the future. URL (last checked 16 August 2012).

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