痰液上清液作为基于下一代测序的体细胞变异分析的替代液体活检标本的效用。
The utility of sputum supernatant as an alternative liquid biopsy specimen for next-generation sequencing-based somatic variation profiling.
作者信息
Qin Ling, Guo Ting, Yang Huaping, Deng Pengbo, Gu Qihua, Liu Chi, Wu Mengping, Lizaso Analyn, Li Bing, Zhang Sa, Chen Zhiqiu, Hu Chengping
机构信息
Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China.
Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, China.
出版信息
Ann Transl Med. 2022 Apr;10(8):462. doi: 10.21037/atm-22-1297.
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% . 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% . 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.
背景
全面基因组分析已成为晚期肺癌管理中的标准临床实践。除了组织和血浆外，其他体液也在被积极探索作为肿瘤DNA的替代来源。本研究调查了非小细胞肺癌（NSCLC）患者诱导痰用于体细胞变异分析的效用。
方法
我们的研究纳入了2018年10月至2019年6月期间诊断为局部晚期至晚期NSCLC的41例未经治疗的患者。使用168基因panel对41例患者匹配的肿瘤、血浆和诱导痰样本进行基于捕获的靶向测序。我们分析了从每种样本类型中检测到的体细胞变异以及匹配样本之间检测到的变异的一致性。一致性率定义为从一种样本类型检测到的变异总数相对于参考样本类型的比例。
结果
以匹配的肿瘤样本作为参考对体细胞变异检测进行比较分析，结果显示血浆的检测率为76.9%，痰上清液的检测率为72.4%，痰沉淀物的检测率为65.7%。相对于肿瘤样本的168个基因，血浆、痰上清液和痰沉淀物的阳性预测值分别为73.3%、80.4%和55.6%，敏感性分别为50.0%、36.9%、31.3%。痰上清液相对于匹配的肿瘤样本的一致性率（69.2%对37.8%；P = 0.031）和最大等位基因分数（P < 0.001）显著高于其匹配的痰沉淀物。痰上清液的检测率与匹配的血浆样本相当（71.4%对67.9%；P = 1.00），但最大等位基因分数显著高于其匹配的血浆样本（P = 0.003）。此外，吸烟者的痰上清液的最大等位基因分数显著高于非吸烟者的痰上清液（P = 0.021）。
结论
我们的研究表明，诱导痰的上清部分是比其沉淀物更好的采样来源，并且与血浆样本表现相当。NSCLC患者的诱导痰可作为基于下一代测序（NGS）的体细胞变异分析的替代介质。
Zotero 插件