Abstract
BackgroundNon-invasive early detection of lung cancer could reduce the number of patients diagnosed with advanced disease, which is associated with a poor prognosis. We analyzed the diagnostic accuracy of a panel of peripheral blood markers in detecting non small cell lung cancer (NSCLC).Methods100 healthy donors and 100 patients with NSCLC were enrolled onto this study. Free circulating DNA, circulating mRNA expression of peptidylarginine deiminase type 4 (PAD4/PADI4), pro-platelet basic protein (PPBP) and haptoglobin were evaluated using a Real-Time PCR-based method.ResultsFree circulating DNA, PADI4, PPBP and haptoglobin levels were significantly higher in NSCLC patients than in healthy donors (p<0.0001, p<0.0001, p = 0.0002 and p = 0.0001, respectively). The fitted logistic regression model demonstrated a significant direct association between marker expression and lung cancer risk. The odds ratios of individual markers were 6.93 (95% CI 4.15–11.58; p<0.0001) for free DNA, 6.99 (95% CI 3.75–13.03; p<0.0001) for PADI4, 2.85 (95% CI 1.71–4.75; p<0.0001) for PPBP and 1.16 (95% CI 1.01–1.33; p = 0.031) for haptoglobin. Free DNA in combination with PPBP and PADI4 gave an area under the ROC curve of 0.93, 95% CI = 0.90–0.97, with sensitivity and specificity over 90%.ConclusionsFree circulating DNA analysis combined with PPBP and PADI4 expression determination appears to accurately discriminate between healthy donors and NSCLC patients. This non-invasive multimarker approach warrants further research to assess its potential role in the diagnostic or screening workup of subjects with suspected lung cancer.
Highlights
Lung cancer is the leading cause of cancer death worldwide and the non-small-cell lung cancer subtype (NSCLC) accounts for about 80% of all cases
None of the markers were correlated with gender, age or smoking habits in either group or with tumor histotype or disease stage in non small cell lung cancer (NSCLC) patients
The relation between marker expression and risk of lung cancer, analyzed by the fitted logistic regression model, showed odds ratios (Ors) of 6.93 for free DNA, 6.99 for PADI4, 2.85 for pro-platelet basic protein (PPBP) and 1.16 for haptoglobin
Summary
Lung cancer is the leading cause of cancer death worldwide and the non-small-cell lung cancer subtype (NSCLC) accounts for about 80% of all cases. Detection could represent a promising strategy to reduce lung cancer mortality. A recent study by the National Lung Screening Trial Research Team reported a 20% reduction in mortality from the use of low-dose spiral computed tomography (CT) in high-risk individuals [3]. The high rate of false positives means that a large proportion of individuals undergo unnecessary follow-up and other diagnostic tests, including biopsy, further increasing costs and health risks associated with screening [3,4,5]. Non-invasive early detection of lung cancer could reduce the number of patients diagnosed with advanced disease, which is associated with a poor prognosis. We analyzed the diagnostic accuracy of a panel of peripheral blood markers in detecting non small cell lung cancer (NSCLC)
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