Plasma cell-free DNA level and its integrity as biomarkers to distinguish non-small cell lung cancer from tuberculosis

Abstract

Aims: The aim of this study was to evaluate the potential clinical value of the plasma cell-free DNA (cfDNA) concentrations and strand integrity as an auxiliary tool for Non-small cell lung cancer (NSCLC) differential diagnosis from tuberculosis in patients with solitary pulmonary nodules detected by computed tomography (CT).

Methods: This research was divided into 3 groups: NSCLC (n=106), tuberculosis (n=105) and healthy controls (n=107). The quantization of plasma DNA fragments was performed by quantitative real-time PCR. Amplifying and quantifying shorter (115bp) and longer (247bp) fragments from abundant genomic ALU repeats.

Results: The level of cfDNA (ALU115) in patients with NSCLC [95.67 (51.28, 238.85) ng/μl] was significantly higher than that in patients with tuberculosis [59.60 (34.25, 102.53) ng/μl, P=0.001] and that in healthy controls [44.66 (24.56, 66.54) ng/μl, P=0.001]. The integrity of cfDNA in patients with NSCLC [5.91(4.14, 7.45)] was also significantly higher than that in patients with tuberculosis [3.85 (2.91, 5.06), P=0.000] and that in healthy controls [2.78(2.18, 4.82), P=0.000]. Receiver-operating characteristic (ROC) curve analysis showed that cfDNA(ALU115) and its integrity could be used as biomarkers to distinguish NSCLC from tuberculosis (AUC=0.628, P=0.001, cut-off values=91.48, sensitivity=57.50%, specificity=64.80%; AUC=0.722, P=0.000, cut-off values=5.54, sensitivity=55.70%, specificity=82.90%, respectively). In addition, the effect of integrity of cfDNA(AUC=0.722) to distinguish NSCLC from tuberculosis was higher than traditional tumor marker Carbohydrate antigen 125(CA125) (AUC=0.626), Neuron-specific enolase(NSE) (AUC=0.716) and Carcino-embryonic antigen(CEA) (AUC=0.589).

Conclusions: cfDNA and its integrity could be used as indicators for identification of NSCLC from tuberculosis. Moreover, the effect of integrity of cfDNA to distinguish NSCLC from tuberculosis was higher than traditional tumor marker CA125, NSE and CEA.

Keywords: Biomarker; Cell-free DNA; Non-small cell lung cancer; Tuberculosis.