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1.
Oncol Lett ; 18(4): 3581-3590, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31516572

RESUMO

The sensitivity and utility of liquid biopsy in clinical practice requires some improvement. The aim of the present study was to improve the detection of epidermal growth factor (EGFR) and cellular tumor antigen p53 (TP53) mutations in liquid biopsies from patients with advanced non-small cell lung cancer (NSCLC) by combining plasma, sputum and urine samples under the same sequencing platform. Plasma, sputum and urine samples, and tumor tissues were obtained from 50 patients with NSCLC and were analyzed using next-generation sequencing. The sensitivity of EGFR-sensitive mutation detection was 84% in plasma, 63% in sputum, 28% in urine, and 91% when combining the three liquid samples (P<0.001). The sensitivity of TP53 mutation detection increased from 87% in plasma to 94% when the three samples were combined (P<0.001). The sensitivity of EGFR or TP53 mutations detection was higher in patients with multiple metastatic sites compared with patients ≤1 metastatic site. In addition, the progression free survival (PFS) rates obtained following analysis of the three samples independently in patients with EGFR sensitizing mutations were similar, and were 9.0 months in the tissue sample, 7.5 months in plasma, 7.9 months in the sputum and 7.3 months in urine (P=0.721). The PFS of patients with TP53 mutations was shorter compared with patients without TP53 mutations and was as follows: Tissue, 8.2 months compared with 10.2 months (P=0.412); plasma, 8.4 months compared with 10.2 months (P=0.466); sputum, 8.3 months compared with 9.1 months (P=0.904); and when combined, 8.8 months compared with 10.3 months (P=0.599). The combination of plasma, sputum and urine increased the detection of EGFR or TP53 mutation with higher sensitivity, and may improve the predictive value of personalized treatment.

2.
Cancer Med ; 8(3): 910-919, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30767431

RESUMO

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).


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Ácidos Nucleicos Livres/genética , Neoplasias Pulmonares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/urina , Ácidos Nucleicos Livres/análise , Ácidos Nucleicos Livres/sangue , Ácidos Nucleicos Livres/urina , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/urina , Masculino , Pessoa de Meia-Idade , Mutação , Metástase Neoplásica , Estudos Prospectivos , Escarro/química , Urinálise
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