Quantitative analysis of individual cell-free DNA concentration before and after penetrating trauma
Cell-free DNA (cfDNA) elevations were remarked in the blood of trauma patients. Published increases refer to comparative values of a healthy control group, ignoring thereby inter- and intra-individual differences under normal conditions. The aim of this study was to quantify cfDNA in patients in the time course of a planned orthopedic surgery, which constitutes the advantage of obtaining individual pre- and post-trauma values for each patient. By this approach, a basis should be established for the potential future application of cfDNA as biomarker for the detection of mild injuries related to volunteer experiments in forensic biomechanics.
Plasma samples of ten patients obtaining knee or hip arthroplasty were analyzed quantitatively for cfDNA by real-time qPCR the day prior operation (Prior), immediately afterwards (Day0), and the day after the surgery (Day1).
Prior values exhibited a broad range, indicating pronounced inter-individual differences in the basic level of cfDNA. After surgery, levels were significantly elevated on both days (Wilcoxon test p = 0.002). In nine patients, highest values were measured on Day0, whereby a fold change of 19 was remarked once. After Day0, values decreased, though they did not reach Prior values until Day1 in nine patients.
Endoprosthesis surgery represents a well-defined trauma scenario for the measurement of individual cfDNA elevations. The analysis of pre- to post-trauma alterations lay the groundwork for the application of cfDNA as biomarker for the detection of minor injuries in the field of forensic biomechanics.
KeywordsCell-free DNA Individual values Trauma Injury Arthroplasty Forensic biomechanics
The authors would like to thank the whole medical personnel that helped with the sample collection as well as the staff at the institute of clinical chemistry at the Campus Grosshadern for their technical support.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in the study were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
- 8.Macher H, Egea-Guerrero JJ, Revuelto-Rey J, Gordillo-Escobar E, Enamorado-Enamorado J, Boza A, Rodriguez A, Molinero P, Guerrero JM, Dominguez-Roldán JM, Murillo-Cabezas F, Rubio A (2012) Role of early cell-free DNA levels decrease as a predictive marker of fatal outcome after severe traumatic brain injury. Clin Chim Acta 414:12–17CrossRefGoogle Scholar
- 9.Lam NY, Rainer TH, Chan LY, Joynt GM, Lo YM (2003) Time course of early and late changes in plasma DNA in trauma patients. Clin Chem 49(8):1286–1291Google Scholar
- 10.Lo YMD, Rainer TH, Chan LYS, Hjelm NM, Cocks RA (2000) Plasma DNA as a prognostic marker in trauma patients. Clin Chem 46(3):319–323Google Scholar
- 12.Wang W, Kong P, Ma G, Li L, Zhu J, Xia T, Xie H, Zhou W, Wang S (2017) Characterization of the release and biological significance of cell-free DNA from breast cancer cell lines. Oncotarget 8(26):43180–43191Google Scholar
- 27.Sanchis S, García-Blas S, Ortega-Paz L, Dantas AP, Rodrígues E, Abellán L, Brugaletta S, Valero E, Minana G, Garabito M, Corchón Á, Núnez J, Carratalá A, Sabaté M (2018) Cell-free DNA and microvascular damage in ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. Rev Española de Cardiol (English Ed.). https://doi.org/10.1016/j.rec.2018.03.005
- 30.Lehmann-Werman R, Neiman D, Zemmour H, Moss J, Magenheim J, Vaknin-Dembinsky A, Rubertsson S, Nellgård B, Blennow K, Zetterberg H, Spalding K, Haller MJ, Wasserfall CH, Schatz DA, Greenbaum CJ, Dorrell C, Grompe M, Zick A, Hubert A, Maoz M, Fendrich V, Bartsch DK, Golan T, Ben Sasson SA, Zamir G, Razin A, Cedar H, Shapiro AMJ, Glaser B, Shemer R, Dor Y (2016) Identification of tissue-specific cell death using methylation patterns of circulating DNA. Proc Natl Acad Sci U S A 113(13):E1826–E1834CrossRefGoogle Scholar
- 32.Dietrich D (2016) Current status and future perspectives of circulating cell-free DNA methylation in clinical diagnostics. Lab Med 40(5):335–343Google Scholar