The impact of non-tumor-derived circulating nucleic acids implicates the prognosis of non-small cell lung cancer

A high level of circulating DNA (cirDNA) in cancer patients has been correlated with poor outcomes. Studies have demonstrated the critical contributions of the tumor-derived cirDNA. In this report, we investigated the roles of the non-tumor-derived cirDNA (nt-cirDNA) in determining the prognosis of non-small cell lung cancer (NSCLC). Plasma samples from 58 advanced NSCLC patients and 52 controls were collected. The nt-cirDNA levels were assessed with qPCR assay to detect the unmethylation status of an epithelial-specific marker, the SHP-1 promoter 2 (unmethylated SHP1P2). Clinicopathological correlations were analyzed. There was a significant increase in the total amount of cirDNA in NSCLC patients compared with controls: 4.3 ng ml(-1) [0.82-49.8] and 2.0 ng ml(-1) [0.03-26.9], respectively (p < 0.01). An increased amount of the unmethylated SHP1P2 in advanced NSCLC was also detected: 3.4 ng ml(-1) [1.2-24.8] versus 2.0 ng ml(-1) [0.03-26.9] in the controls (p = 0.026). Survival analyses revealed that high levels of total cirDNA and unmethylated SHP1P2 were significantly associated with decreased survival. However, the total cirDNA had a better prognostic correlation than the unmethylated SHP1P2. Multivariate analysis identified total cirDNA (p = 0.004) and systemic treatment (p = 0.002) as independent prognostic parameters. The level of total cirDNA in NSCLC is an important prognostic parameter that demonstrates the contributions from both tumor-derived sources and non-tumor-derived sources.