Circulating deoxyribonucleic Acid as prognostic marker in non-small-cell lung cancer patients undergoing chemotherapy.
OBJECTIVE
Circulating cell-free DNA is present in increased amounts in the blood of cancer patients, but the clinical relevance of this phenomenon remains unclear. We conducted a clinical study to assess the value of circulating DNA as a prognostic marker in patients with non-small-cell lung cancer (NSCLC).


METHODS
A standard protocol for the quantification of circulating DNA by real-time polymerase chain reaction was set up and validated at two oncology units. One hundred eighty-five informed patients with NSCLC and 46 healthy controls were included in the study. DNA concentrations were determined in paired plasma and serum samples and analyzed for a relationship with leukocyte counts and lactate dehydrogenase (LDH) levels. DNA concentrations in healthy controls and in patients were compared, and cutoff levels for plasma and serum DNA were determined. Patient survival was analyzed relative to baseline DNA concentrations, and the relationship between tumor responses and changes in DNA concentrations was assessed in patients receiving chemotherapy.


RESULTS
We found a significant correlation between increased plasma DNA concentrations and elevated LDH levels (P = .009), advanced tumor stage (P < .003), and poor survival (P < .001). Tumor progression after chemotherapy was significantly (P = .006) associated with increasing plasma DNA concentrations. Serum DNA concentrations strongly correlated (P < .001) with leukocyte counts.


CONCLUSIONS
Our data demonstrate that quantification of plasma DNA is an accurate technique amenable to standardization, which might complement current methods for the prediction of patient survival. This approach might be considered for evaluation in large prospective studies.
Zurich University Hospital, Clinic and Policlinic of Oncology, Laboratory of Molecular Oncology, Haeldeliweg 4, 8044 Zurich, Switzerland. annemarie.ziegler@usz.ch
Oliver
O
Gautschi
Colette
C
Bigosch
Barbara
B
Huegli
Monika
M
Jermann
Arthur
A
Marx
Eveline
E
Chassé
Daniel
D
Ratschiller
Walter
W
Weder
Markus
M
Joerger
Daniel C
DC
Betticher
Rolf A
RA
Stahel
Annemarie
A
Ziegler
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D004273:DNA, Neoplasm / Q000097:blood*; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D007958:Leukocyte Count; D008175:Lung Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D015996:Survival Rate
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D007770:L-Lactate Dehydrogenase