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

Ling Qin; Ting Guo; Huaping Yang; Pengbo Deng; Qihua Gu; Chi Liu; Mengping Wu; Analyn Lizaso; Bing Li; Sa Zhang; Zhiqiu Chen; Chengping Hu

doi:10.21037/atm-22-1297

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

Ann Transl Med. 2022 Apr;10(8):462. doi: 10.21037/atm-22-1297.

Authors

Ling Qin¹, Ting Guo¹, Huaping Yang¹, Pengbo Deng¹, Qihua Gu¹, Chi Liu², Mengping Wu², Analyn Lizaso³, Bing Li³, Sa Zhang³, Zhiqiu Chen³, Chengping Hu¹

Affiliations

¹ Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China.
² Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, China.
³ Burning Rock Biotech, Guangzhou, China.

Abstract

Background: Comprehensive genomic profiling has become 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. This study investigated the utility of induced sputum obtained from patients with non-small-cell lung cancer (NSCLC) for somatic variation profiling.

Methods: Our study included 41 treatment-naïve patients diagnosed with locally advanced to advanced NSCLC between October 2018 and June 2019. Capture-based targeted sequencing was performed on matched tumor, plasma, and induced sputum samples of 41 patients using a 168-gene panel. We analyzed the somatic variations detected from each sample type and the concordance of variations detected between matched samples. The concordance rate was defined as the proportion of the total number of variations detected from one sample type relative to the reference sample type.

Results: Comparative analysis on the somatic variation detection using matched tumor samples as a 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 their matched sputum-sediments. Sputum-supernatants had comparable detection rates (71.4% vs. 67.9%; P=1.00) 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 performs comparably to plasma samples. Induced sputum from NSCLC patients could serve as an alternative media for next-generation sequencing (NGS)-based somatic variation profiling.

Keywords: Sputum; alternative specimen; molecular testing; non-small-cell lung cancer (NSCLC); tumor DNA.