The utility of sputum supernatant as an alternative liquid biopsy specimen for next-generation sequencing-based genomic profiling

Background Comprehensive mutation profiling has become a standard clinical practice in the management of advanced lung cancer. In addition to tissue and plasma, other body fluids are also being actively explored as alternative sources of tumor DNA. In this study, we investigated the potential of induced sputum obtained from patients with non-small cell lung cancer (NSCLC) for mutation profiling. Methods Capture-based targeted sequencing was performed on matched tumor, plasma, and induced sputum samples of 41 treatment-naïve patients with NSCLC using 168 gene panel. Results Comparative analysis on the mutation detection using matched tumor sample as reference revealed detection rates of 76.9% for plasma, 72.4% for sputum-supernatant, and 65.7% for sputum-sediment samples. Plasma, sputum-supernatant, and sputum-sediment achieved positive predictive values of 73.3%, 80.4%, and 55.6% and sensitivities of 50.0%, 36.9%, 31.3%, respectively, relative to tumor samples for 168 genes. Sputum-supernatants had significantly higher concordance rates relative to matched tumor samples (69.2% vs 37.8%; P = 0.031) and maximum allelic fraction (P < 0.001) than its matched sputum-sediments. Sputum-supernatants had comparable detection rates (71.4% vs. 67.9%; P = 1) but with significantly higher maximum allelic fraction than their matched plasma samples (P = 0.003). Furthermore, sputum-supernatant from smokers had a significantly higher maximum allelic fraction than sputum-supernatant from non-smokers (P = 0.021). Conclusions Our study demonstrated that supernatant fraction from induced sputum is a better sampling source than its sediment and has comparable performance as plasma samples. Induced sputum from NSCLC patients could serve as an alternative media for next-generation sequencing-based mutation profiling.