Circulating plasma DNA as diagnostic biomarker in non-small cell lung cancer.
OBJECTIVE
The presence of circulating DNA in plasma of patients with malignant neoplasm has been a known fact for over 30 years. Since then, the concentration of free circulating plasma DNA has been studied as well as the genetic alterations and epigenetic alterations of tumour DNA of patients that suffer from various types of tumours. The analysis of circulating plasma DNA may be a useful marker to get an early diagnosis on malignant neoplasms. This study has been specifically designed to validate the quantification of circulating DNA in order to design a test useful for the early identification of non-small cell lung cancer patients and the monitoring of lung cancer progression. A second aim of this work is the sensibility and specificity evaluation of such method for future applications.


METHODS
The quantity of plasma DNA was determined using quantitative Real-Time PCR with amplification of the human telomerase reverse transcriptase (hTERT) gene in 151 patients that suffer from lung cancer and 79 healthy controls. The performance of the test was evaluated with a ROC curve. The relationship between the DNA concentration and main demographic, clinical and pathological variables was examined with logistic regression models as well as multiple linear regression models.


RESULTS
The concentration of circulating plasma DNA was about four times higher in patients with lung cancer with respect to the controls (12.8 vs 2.9 ng/mL). The area under the ROC curve was 0.79 (95% CI, 0.710-0.83). The concentration of circulating DNA proved to be an important risk factor for the presence of the illness and a prognostic index in the follow-up.


CONCLUSIONS
The use of quantitative Real-Time PCR revealed that higher values of circulating DNA can be found in patients with lung neoplasm compared to the healthy controls. This could have practical implications such as the use in screening programs and a possible prognostic significance in the follow-up.
Paci
Massimiliano
M
Division of Thoracic Surgery, Azienda Ospedaliera Santa Maria Nuova, Viale Risorgimento 80, 42100 Reggio Emilia, Italy. paci.massimiliano@asmn.re.it
Maramotti
Sally
S
Bellesia
Enrica
E
Formisano
Debora
D
Albertazzi
Laura
L
Ricchetti
Tommaso
T
Ferrari
Guglielmo
G
Annessi
Valerio
V
Lasagni
Daniela
D
Carbonelli
Cristiano
C
De Franco
Salvatore
S
Brini
Maria
M
Sgarbi
Giorgio
G
Lodi
Renzo
R
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000175:diagnosis; D016022:Case-Control Studies; D004273:DNA, Neoplasm / Q000097:blood*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012372:ROC Curve; D012680:Sensitivity and Specificity; D019098:Telomerase / Q000097:blood / Q000235:genetics
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C509186:TERT protein, human; D019098:Telomerase