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Erschienen in: International Journal of Legal Medicine 2/2019

16.10.2018 | Original Article

Quantitative analysis of individual cell-free DNA concentration before and after penetrating trauma

verfasst von: Katrin Brodbeck, Stefanie Kern, Sylvia Schick, Arnd Steinbrück, Michael Schwerer, Birgit Bayer, Katja Anslinger, Steffen Peldschus

Erschienen in: International Journal of Legal Medicine | Ausgabe 2/2019

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Abstract

Introduction

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.

Methods

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).

Results

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.

Conclusion

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.
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Literatur
1.
Zurück zum Zitat Muggenthaler H, von Merten K, Peldschus S, Holley S, Adamec J, Praxl N, Graw M (2008) Experimental tests for the validation of active numerical human models. Forensic Sci Int 177(2–3):184–191CrossRef Muggenthaler H, von Merten K, Peldschus S, Holley S, Adamec J, Praxl N, Graw M (2008) Experimental tests for the validation of active numerical human models. Forensic Sci Int 177(2–3):184–191CrossRef
2.
Zurück zum Zitat Bohnert M, Baumgartner R, Pollak S (2000) Spectrophotometric evaluation of the colour of intra- and subcutaneous bruises. Int J Legal Med 113(6):343–348CrossRef Bohnert M, Baumgartner R, Pollak S (2000) Spectrophotometric evaluation of the colour of intra- and subcutaneous bruises. Int J Legal Med 113(6):343–348CrossRef
3.
Zurück zum Zitat Lombardi M, Canter J, Patrick P a, Altman R (2015) Is fluorescence under an alternate light source sufficient to accurately diagnose subclinical bruising? J Forensic Sci 60(2):444–449CrossRef Lombardi M, Canter J, Patrick P a, Altman R (2015) Is fluorescence under an alternate light source sufficient to accurately diagnose subclinical bruising? J Forensic Sci 60(2):444–449CrossRef
4.
Zurück zum Zitat Rowan P, Hill M, Gresham G a, Goodall E, Moore T (2010) The use of infrared aided photography in identification of sites of bruises after evidence of the bruise is absent to the naked eye. J Forensic Legal Med 17(6):293–297CrossRef Rowan P, Hill M, Gresham G a, Goodall E, Moore T (2010) The use of infrared aided photography in identification of sites of bruises after evidence of the bruise is absent to the naked eye. J Forensic Legal Med 17(6):293–297CrossRef
5.
Zurück zum Zitat Helm T, Bir C, Chilstrom M, Claudius I (2016) Ultrasound characteristics of bruises and their correlation to cutaneous appearance. Forensic Sci Int 266:160–163CrossRef Helm T, Bir C, Chilstrom M, Claudius I (2016) Ultrasound characteristics of bruises and their correlation to cutaneous appearance. Forensic Sci Int 266:160–163CrossRef
6.
Zurück zum Zitat Timmermans K, Kox M, Vaneker M, van den Berg M, John A, van Laarhoven A, van der Hoeven H, Scheffer GJ, Pickkers P (2016) Plasma levels of danger-associated molecular patterns are associated with immune suppression in trauma patients. Intensive Care Med 42(4):551–561CrossRef Timmermans K, Kox M, Vaneker M, van den Berg M, John A, van Laarhoven A, van der Hoeven H, Scheffer GJ, Pickkers P (2016) Plasma levels of danger-associated molecular patterns are associated with immune suppression in trauma patients. Intensive Care Med 42(4):551–561CrossRef
7.
Zurück zum Zitat Ren B, Liu F, Xu F, He J, Zhu H, Zou G (2013) Is plasma cell-free DNA really a useful marker for diagnosis and treatment of trauma patients? Clin Chim Acta 424:109–113CrossRef Ren B, Liu F, Xu F, He J, Zhu H, Zou G (2013) Is plasma cell-free DNA really a useful marker for diagnosis and treatment of trauma patients? Clin Chim Acta 424:109–113CrossRef
8.
Zurück zum Zitat 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 414:12–17CrossRef 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 414:12–17CrossRef
9.
Zurück zum Zitat 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):1286–1291 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):1286–1291
10.
Zurück zum Zitat Lo YMD, Rainer TH, Chan LYS, Hjelm NM, Cocks RA (2000) Plasma DNA as a prognostic marker in trauma patients. Clin Chem 46(3):319–323CrossRef Lo YMD, Rainer TH, Chan LYS, Hjelm NM, Cocks RA (2000) Plasma DNA as a prognostic marker in trauma patients. Clin Chem 46(3):319–323CrossRef
11.
Zurück zum Zitat Thierry AR, El Messaoudi S, Gahan PB, Anker P, Stroun M (2016) Origins, structures, and functions of circulating DNA in oncology. Cancer Metastasis Rev 35(3):347–376CrossRef Thierry AR, El Messaoudi S, Gahan PB, Anker P, Stroun M (2016) Origins, structures, and functions of circulating DNA in oncology. Cancer Metastasis Rev 35(3):347–376CrossRef
12.
Zurück zum Zitat 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):43180–43191PubMedPubMedCentral 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):43180–43191PubMedPubMedCentral
13.
Zurück zum Zitat Lee T, LeShane ES, Messerlian GM, Canick JA, Farina A, Heber WW, Bianchi DW (2002) Down syndrome and cell-free fetal DNA in archived maternal serum. Am J Obstet Gynecol 187(5):1217–1221CrossRef Lee T, LeShane ES, Messerlian GM, Canick JA, Farina A, Heber WW, Bianchi DW (2002) Down syndrome and cell-free fetal DNA in archived maternal serum. Am J Obstet Gynecol 187(5):1217–1221CrossRef
14.
Zurück zum Zitat Lo DYM, Tein MSC, Lau TK, Haines CJ (1998) Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am J Hum Genet 62(4):768–775CrossRef Lo DYM, Tein MSC, Lau TK, Haines CJ (1998) Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am J Hum Genet 62(4):768–775CrossRef
15.
Zurück zum Zitat Wang C, Stanciu CE, Ehrhardt CJ, Yadavalli VK (2017) Nanoscale characterization of forensically relevant epithelial cells and surface associated extracellular DNA. Forensic Sci Int 277:252–258CrossRef Wang C, Stanciu CE, Ehrhardt CJ, Yadavalli VK (2017) Nanoscale characterization of forensically relevant epithelial cells and surface associated extracellular DNA. Forensic Sci Int 277:252–258CrossRef
16.
Zurück zum Zitat Taki T, Kibayashi K (2015) Characterization of cellular and extracellular DNA in saliva. Leg Med (Tokyo) 17(6):471–474CrossRef Taki T, Kibayashi K (2015) Characterization of cellular and extracellular DNA in saliva. Leg Med (Tokyo) 17(6):471–474CrossRef
17.
Zurück zum Zitat McIlroy DJ, Bigland M, White AE, Hardy BM, Lott N, Smith DW, Balogh ZJ (2015) Cell necrosis-independent sustained mitochondrial and nuclear DNA release following trauma surgery. J Trauma Acute Care Surg 78(2):282–288CrossRef McIlroy DJ, Bigland M, White AE, Hardy BM, Lott N, Smith DW, Balogh ZJ (2015) Cell necrosis-independent sustained mitochondrial and nuclear DNA release following trauma surgery. J Trauma Acute Care Surg 78(2):282–288CrossRef
18.
Zurück zum Zitat Wijeratne S, Butt A, Burns S, Sherwood K, Boyd O, Swaminathan R (2004) Cell-free plasma DNA as a prognostic marker in intensive treatment unit patients. Ann N Y Acad Sci 1022:232–238CrossRef Wijeratne S, Butt A, Burns S, Sherwood K, Boyd O, Swaminathan R (2004) Cell-free plasma DNA as a prognostic marker in intensive treatment unit patients. Ann N Y Acad Sci 1022:232–238CrossRef
19.
Zurück zum Zitat Fox A, Gal S, Fisher N, Smythe J, Wainscoat J, Tyler MPH, Watt SM, Harris a L (2008) Quantification of circulating cell-free plasma DNA and endothelial gene RNA in patients with burns and relation to acute thermal injury. Burns 34(6):809–816CrossRef Fox A, Gal S, Fisher N, Smythe J, Wainscoat J, Tyler MPH, Watt SM, Harris a L (2008) Quantification of circulating cell-free plasma DNA and endothelial gene RNA in patients with burns and relation to acute thermal injury. Burns 34(6):809–816CrossRef
20.
Zurück zum Zitat Shaked G, Douvdevani A, Yair S, Zlotnik A, Czeiger D (2014) The role of cell-free DNA measured by a fluorescent test in the management of isolated traumatic head injuries. Scand J Trauma Resusc Emerg Med 22(1):21CrossRef Shaked G, Douvdevani A, Yair S, Zlotnik A, Czeiger D (2014) The role of cell-free DNA measured by a fluorescent test in the management of isolated traumatic head injuries. Scand J Trauma Resusc Emerg Med 22(1):21CrossRef
21.
Zurück zum Zitat Rhodes A, Wort SJ, Thomas H, Collinson P, David ED (2006) Plasma DNA concentration as a predictor of mortality and sepsis in critically ill patients. Crit Care 10(2):1–7CrossRef Rhodes A, Wort SJ, Thomas H, Collinson P, David ED (2006) Plasma DNA concentration as a predictor of mortality and sepsis in critically ill patients. Crit Care 10(2):1–7CrossRef
22.
Zurück zum Zitat Szpechcinski A, Chorostowska-Wynimko J, Kupis W, Maszkowska-Kopij K, Dancewicz M, Kowalewski J, Orlowski T (2012) Quantitative analysis of free-circulating DNA in plasma of patients with resectable NSCLC. Expert Opin Biol Ther 12(sup1):S3–S9CrossRef Szpechcinski A, Chorostowska-Wynimko J, Kupis W, Maszkowska-Kopij K, Dancewicz M, Kowalewski J, Orlowski T (2012) Quantitative analysis of free-circulating DNA in plasma of patients with resectable NSCLC. Expert Opin Biol Ther 12(sup1):S3–S9CrossRef
23.
Zurück zum Zitat El Messaoudi S, Rolet F, Mouliere F, Thierry AR (2013) Circulating cell free DNA: preanalytical considerations. Clin Chim Acta 424:222–230CrossRef El Messaoudi S, Rolet F, Mouliere F, Thierry AR (2013) Circulating cell free DNA: preanalytical considerations. Clin Chim Acta 424:222–230CrossRef
24.
Zurück zum Zitat Mauger F, Dulary C, Daviaud C, Deleuze JF, Tost J (2015) Comprehensive evaluation of methods to isolate, quantify, and characterize circulating cell-free DNA from small volumes of plasma. Anal Bioanal Chem 407(22):6873–6878CrossRef Mauger F, Dulary C, Daviaud C, Deleuze JF, Tost J (2015) Comprehensive evaluation of methods to isolate, quantify, and characterize circulating cell-free DNA from small volumes of plasma. Anal Bioanal Chem 407(22):6873–6878CrossRef
25.
Zurück zum Zitat Xie J, Yang J, Hu P (2018) Acute myocardial infarction patients show strong variations in circulating cell free DNA and correlated to clinical manifestations. Am J Med Sci 356:121–129CrossRef Xie J, Yang J, Hu P (2018) Acute myocardial infarction patients show strong variations in circulating cell free DNA and correlated to clinical manifestations. Am J Med Sci 356:121–129CrossRef
26.
Zurück zum Zitat Biró O, Hajas O, Nagy-Baló E, Soltész B, Csanádi Z, Bálint N (2018) Relationship between cardiovascular diseases and circulating cell-free nucleic acids in human plasma. Biomark Med 12:891–905CrossRef Biró O, Hajas O, Nagy-Baló E, Soltész B, Csanádi Z, Bálint N (2018) Relationship between cardiovascular diseases and circulating cell-free nucleic acids in human plasma. Biomark Med 12:891–905CrossRef
27.
Zurück zum Zitat 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 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 
28.
Zurück zum Zitat Wang L, Xie L, Zhang Q, Cai X, Tang Y, Wang L, Hang T, Liu J, Gong J (2015) Plasma nuclear and mitochondrial DNA levels in acute myocardial infarction patients. Coron Artery Dis 26(4):296–300CrossRef Wang L, Xie L, Zhang Q, Cai X, Tang Y, Wang L, Hang T, Liu J, Gong J (2015) Plasma nuclear and mitochondrial DNA levels in acute myocardial infarction patients. Coron Artery Dis 26(4):296–300CrossRef
29.
Zurück zum Zitat Chang CPY, Chia RH, Wu TL, Tsao KC, Sun CF, Wu JT (2003) Elevated cell-free serum DNA detected in patients with myocardial infarction. Clin Chim Acta 327(1–2):95–101CrossRef Chang CPY, Chia RH, Wu TL, Tsao KC, Sun CF, Wu JT (2003) Elevated cell-free serum DNA detected in patients with myocardial infarction. Clin Chim Acta 327(1–2):95–101CrossRef
30.
Zurück zum Zitat 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–E1834CrossRef 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–E1834CrossRef
31.
Zurück zum Zitat Zemmour H, Planer D, Magenheim J, Moss J, Neiman D, Gilon D, Korach A, Glaser B, Shemer R, Landesberg G, Dor Y (2018) Non-invasive detection of human cardiomyocyte death using methylation patterns of circulating DNA. Nat Commun 9(1):1443CrossRef Zemmour H, Planer D, Magenheim J, Moss J, Neiman D, Gilon D, Korach A, Glaser B, Shemer R, Landesberg G, Dor Y (2018) Non-invasive detection of human cardiomyocyte death using methylation patterns of circulating DNA. Nat Commun 9(1):1443CrossRef
32.
Zurück zum Zitat Dietrich D (2016) Current status and future perspectives of circulating cell-free DNA methylation in clinical diagnostics. Lab Med 40(5):335–343 Dietrich D (2016) Current status and future perspectives of circulating cell-free DNA methylation in clinical diagnostics. Lab Med 40(5):335–343
Metadaten
Titel
Quantitative analysis of individual cell-free DNA concentration before and after penetrating trauma
verfasst von
Katrin Brodbeck
Stefanie Kern
Sylvia Schick
Arnd Steinbrück
Michael Schwerer
Birgit Bayer
Katja Anslinger
Steffen Peldschus
Publikationsdatum
16.10.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
International Journal of Legal Medicine / Ausgabe 2/2019
Print ISSN: 0937-9827
Elektronische ISSN: 1437-1596
DOI
https://doi.org/10.1007/s00414-018-1945-y

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