Create successful ePaper yourself
Turn your PDF publications into a flip-book with our unique Google optimized e-Paper software.
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