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Increased plasma DNA concentration in patients with<br />

lung cancer<br />

Darko ^erne 1 , Miha Sok 2 , Jana Luka~ Bajalo 3<br />

1<br />

University of Primorska, College of Health Care Isola, Isola, Slovenia; 2 Medical Centre<br />

Ljubljana, Department of Thoracic Surgery, Ljubljana, Slovenia; 3 University of Ljubljana,<br />

Faculty of Pharmacy, Ljubljana, Slovenia<br />

Background: Concentration of cell-free DNA in plasma (plasma DNA) was reported<br />

to be elevated in patients with various tumors, autoimmune diseases, traumatic<br />

conditions (stroke, multiple trauma, sepsis), other benign disorders (diabetes) and<br />

prenatal complications. Increased level was proposed as a novel tumor marker<br />

reflecting tumor cell turnover (lysis of circulating cancer cells, tumor necrosis and<br />

apoptosis) or spontaneous and active release from cancer cells.<br />

Aim of the study: Our aim was to determine reference values of plasma DNA<br />

concentration in apparently health subjects and to test the hypothesis that patient<br />

with lung cancer have increased values when compared to the reference group.<br />

To test the hypothesis we measured plasma DNA concentrations with reagents<br />

Nucleospin® and PicoGreen® in 51 apparently health subjects and in 29 patients<br />

with lung cancer. In 10 patients blood was taken on a day of tumor resection and in<br />

19 patients 1-3 months after operation.<br />

Results: In healthy subjects acute and chronic diseases were excluded clinically,<br />

and on the basis of patient history and values of fundamental laboratory tests<br />

within reference range. The median (25 th percentiles; 75 th percentiles) {minimum;<br />

maximum} of plasma DNA concentrations was 2.85 (2.05; 4.30) {0.1; 15.85} µg/L.<br />

The reference range was from 0.30 to 9.75 µg/L. In patients concentrations of DNA<br />

in plasma on a day of operation were 2.47 times higher (medians 7.05 vs. 2.85 µg/L;<br />

p = 0.<strong>02</strong>70) and after operation 3.72 times higher (medians 10.60 vs. 2.85 µg/L;<br />

p < 0.0001) when compared to the health subjects. No difference was found between<br />

the both subgroups of patients. Furthermore, plasma DNA concentration did not<br />

correlate with a stage of cancer and did not differ within individual histological<br />

type of tumor, neither within both subgroups separately, nor in all patients gathered<br />

as one group. Plasma concentration higher than 4.45 µg/L distinguished patients<br />

(considered as one group) from apparently health subjects with the sensitivity of<br />

89.7 % and specificity of 80.4 %. The area under ROC curve was 0.870 with 95 % of<br />

confidence limit from 0.776 to 0.934.<br />

Discussion: Patients with lung cancer have increased plasma DNA concentration<br />

when compared to apparently healthy subjects. Elevated plasma DNA concentration<br />

lacks disease specificity, but may be beneficially used for screening the patients at<br />

high risk for lung cancer.<br />

l4867

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