Abstract
A non-invasive test to facilitate the diagnosis of non-small cell lung cancer (NSCLC) and idiopathic pulmonary fibrosis (IPF) is still not available and represents an important goal. Forty-eight patients with stage I NSCLC, 45 with IPF, 30 with other idiopathic interstitial pneumonias (IIPs) including idiopathic non-specific interstitial pneumonia (NSIP) and chronic hypersensitivity pneumonitis (HP), 35 with diffuse non-malignant disease and 30 healthy donors were enrolled onto the study. Free circulating (fc)DNA and MMP-7 levels were evaluated by Real Time PCR and ELISA, respectively. Median fcDNA levels were similar in NSCLC (127 ng/mL, range 23.6–345 ng/mL) and IPF (106 ng/mL, range 22–224 ng/mL) patients, and significantly lower in IIPs patients, in individuals with other diseases and in healthy donors (p < 0.05). Conversely, median MMP-7 values were significantly higher in IPF patients (9.10 ng/mL, range 3.88–19.72 ng/mL) than in those with NSCLC (6.31 ng/mL, range 3.38–16.36 ng/mL; p < 0.0001), NSIP (6.50 ng/mL, range 1.50–22.47 ng/mL; p = 0.007), other diseases (5.41 ng/mL, range 1.78–15.91, p < 0.0001) or healthy donors (4.35 ng/mL, range 2.45–7.23; p < 0.0001). Serum MMP-7 levels seem to be capable of distinguishing IPF patients from those with any other lung disease. fcDNA levels were similar in NSCLC and IPF patients, confirming its potential role as a biomarker, albeit non-specific, for the differential diagnosis of NSCLC.
Highlights
Non-small cell lung cancer (NSCLC) and idiopathic pulmonary fibrosis (IPF) represent two of the most serious lung diseases
A high area under the curve (AUC) value was observed in discriminating between non-small cell lung cancer (NSCLC) patients and healthy donors (AUC 0.90; 95% confidence intervals (95% CI) 0.83–0.98), whereas the value decreased when individuals with other lung diseases were included in the control group (AUC 0.75; 95% CI 0.67–0.84) (Figure 3A,B)
Our results confirmed the role of matrix metalloproteinases (MMPs)-7 as a diagnostic marker for IPF and highlighted the relevance of free circulating DNA (fcDNA) in both NSCLC and IPF diagnosis. fcDNA levels could represent a promising non-invasive diagnostic marker to discriminate between early stage NSCLC and other non-neoplastic pulmonary diseases, and to distinguish IPF patients from those with other interstitial pneumonias (IIPs)
Summary
Non-small cell lung cancer (NSCLC) and idiopathic pulmonary fibrosis (IPF) represent two of the most serious lung diseases. We previously demonstrated that free circulating DNA (fcDNA) levels are higher in IPF patients than in those with other interstitial lung diseases [7]. IPF is characterized by diffuse interstitial inflammation, fibroblast proliferation and accelerated remodeling of extracellular matrix (ECM), all of which result in irreversible destruction of the fine architecture of the lung [3,4,5]. It has been shown that serum MMP-7 levels are higher in IPF patients, including asymptomatic ones, than in individuals with other non-malignant lung diseases, indicating its potential usefulness as a marker for the early. We aimed to analyze MMP-7 and fcDNA serum levels in patients with different malignant and non-malignant lung diseases, including NSCLC, IPF and other IIPs including non-specific interstitial pneumonia (NSIP) and chronic hypersensitivity pneumonitis (HP)
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