Urine cell-free DNA as a promising biomarker for early detection of non-small cell lung cancer.

Abstract

BackgroundWhile blood‐derived cell‐free DNA has been shown to be a candidate biomarker able to provide diagnostic and prognostic insight in cancer patients, little is known regarding the potential application of urine cell‐free DNA (ucfDNA) in diagnosis of cancer. Thus, the aim of this study was to investigate ucfDNA concentration and integrity index as potential biomarkers for early detection of non‐small‐cell lung cancer (NSCLC).MethodsUrine samples were collected from 35 healthy controls and 55 NSCLC patients at various tumor node metastasis (TNM) stages. Two long interspersed nuclear element 1 (LINE1) fragments (LINE1‐97 and 266 bp) were quantified via quantitative real‐time PCR (qPCR). DNA integrity index was calculated as the ratio of LINE1‐266/LINE‐97.ResultsLINE1 fragments concentrations of ucfDNA (LINE1‐97, 266 bp) were significantly higher in NSCLC patients with stage III/IV than in stage I/II and in healthy controls. The receiver operating characteristic (ROC) curves for discriminating patients with stage III/IV from healthy controls had areas under the curves (AUC) of 0.84 and 0.886, respectively. Moreover, ucfDNA integrity LINE1‐266/97 was significantly higher in patients with stage III/IV than in stage I/II and in healthy controls. The AUC of ROC curve for discriminating patients with stage III/IV from healthy controls was 0.800. Furthermore, LINE1‐266 fragment concentration was significantly higher in lymph node metastasis (LNM)‐positive patients relative to LNM‐negative patients. The ROC curve for discriminating LNM‐positive from LNM‐negative patients had an AUC of 0.822.ConclusionUcfDNA could serve as a promising biomarker for early detection of NSCLC.