Differences in the genomic profiles of cell‐free DNA between plasma, sputum, urine, and tumor tissue in advanced NSCLC

Abstract

Liquid biopsy has provided an efficient way for detection of gene alterations in advanced non‐small‐cell lung cancer (NSCLC). However, the correlation between systematic determination of somatic genomic alterations in liquid biopsy and tumor biopsy still remained unclear, and the concordance rate between cell‐free DNA (cfDNA) and matched tumor tissue DNA needs to be increased. A prospective study was performed to detect differences in genetic profiles of cfDNA in sputum, plasma, urine, and tumor tissue from 50 advanced NSCLC patients in parallel by the same next‐generation sequencing (NGS) platform. Driver genes alterations were identified in cfDNA sample and matched tumor sample, with an overall concordance rate of 86% in plasma cfDNA, 74% in sputum cfDNA, 70% in urine cfDNA, and 90% in cfDNA of combination of plasma, sputum, and urine. And the concordant rate of cfDNA in sputum in patients with smoking history was higher than that in patients without history of smoking (89% vs. 66%, P = 0.033) and equal to that in plasma cfDNA of the smoking patients (89% vs. 89%). In conclusion, sputum cfDNA can be considered as an alternative medium to liquid biopsy, while the complementarity of genomic profiles in cfDNA among plasma, sputum, and urine was beneficial to detect more diver genes alterations and improve the utility of liquid biopsy in advanced NSCLC (Liquid Biopsy for Detection of Driver Mutation in NSCLC; NCT02778854).

The Value of Next-Generation Sequencing for Treatment in Non-Small Cell Lung Cancer Patients: The Observational, Real-World Evidence in China

“…Library fragment size was determined by an Agilent Technologies (Palo Alto, CA) 2100 Bioanalyzer. e target-enriched library was then sequenced on HiSeq4000 NGS platforms (Illumina) [13].…”

From Traditional Histology to Next-Generation Pathology: A Review of The Workflow for the Characterisation and Molecular Profiling of Non-Small Cell Lung Cancer Samples

“…94 Different experiences focalised the attention on sputum to investigate EGFR status in NSCLC patients. In a large series (N=50), Wu et al 95 identified a high concordance rate between sputum and tissue samples (74%). 95 Hubers et al 96 reported a specificity of 100% but low sensitivity of 50%.…”

“…In a large series (N=50), Wu et al 95 identified a high concordance rate between sputum and tissue samples (74%). 95 Hubers et al 96 reported a specificity of 100% but low sensitivity of 50%. In addition to predictive purposes, sputum could also be adopted for diagnostic aims and for secondary prevention.…”

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

“…Malignant non-blood biological uids that are in close contact with the tumors, including pleural effusion, ascites, and cerebrospinal uid, are gaining attention as specimens for molecular testing due to their effectiveness in re ecting tumor genomic pro les [9][10][11][12]. Meanwhile, other easily accessible biological uids including sputum that likely contain tumor-derived DNA are being actively explored for mutation detection [9,[13][14][15][16][17]. Sputum has been explored in the detection of genetic and epigenetic alterations in patients with various stages of lung cancer and in cancer-free chronic smokers who are at higher risk of developing lung cancer [9,13,[15][16][17][18][19][20][21][22][23][24][25][26][27].…”

“…Meanwhile, other easily accessible biological uids including sputum that likely contain tumor-derived DNA are being actively explored for mutation detection [9,[13][14][15][16][17]. Sputum has been explored in the detection of genetic and epigenetic alterations in patients with various stages of lung cancer and in cancer-free chronic smokers who are at higher risk of developing lung cancer [9,13,[15][16][17][18][19][20][21][22][23][24][25][26][27]. These studies consistently demonstrate that induced sputum samples contain circulating cellfree DNA derived from the lungs and lower respiratory tract and are attractive candidate liquid biopsy media for lung cancer diagnosis [13,[15][16][17][18][19][20][21][22][23][24][25][26][27].…”