RESUMO
Circulating tumor DNA (ctDNA) isolated from peripheral blood has recently been shown to be an alternative source to detect gene mutations in primary tumors; however, most previous studies have focused on advanced stage cancers, and few have evaluated ctDNA detection in early-stage lung cancer. In the present study, blood and tumor samples were collected prospectively from 58 early-stage non-small lung cancer (NSCLC) patients (stages IA, IB, and IIA) and a targeted sequencing approach was used to detect somatic driver mutations in matched tumor DNA (tDNA) and plasma ctDNA. We identified frequent driver mutations in plasma ctDNA and tDNA in EGFR, KRAS, PIK3CA, and TP53, and less frequent mutations in other genes, with an overall study concordance of 50.4% and sensitivity and specificity of 53.8% and 47.3%, respectively. Cell-free (cfDNA) concentrations were found to be significantly associated with some clinical features, including tumor stage and subtype. Importantly, the presence of cfDNA had a higher positive predictive value than that of currently used protein tumor biomarkers. This study demonstrates the feasibility of identifying plasma ctDNA mutations in the earliest stage lung cancer patients via targeted sequencing, demonstrating a potential utility of targeted sequencing of ctDNA in the clinical management of NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , DNA Tumoral Circulante/sangue , Neoplasias Pulmonares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Glicosídicos Associados a Tumores/sangue , Biomarcadores Tumorais/sangue , Antígeno Ca-125/sangue , Carcinoma Pulmonar de Células não Pequenas/genética , DNA Tumoral Circulante/química , Classe I de Fosfatidilinositol 3-Quinases/genética , DNA de Neoplasias/sangue , DNA de Neoplasias/química , Receptores ErbB/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Pulmonares/genética , Masculino , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Proteínas Proto-Oncogênicas p21(ras)/genética , Análise de Sequência de DNA , Proteína Supressora de Tumor p53/genéticaRESUMO
Non-small cell lung cancers (NSCLC) have unique mutation patterns, and some of these mutations may be used to predict prognosis or guide patient treatment. Mutation profiling before and during treatment often requires repeated tumor biopsies, which is not always possible. Recently, cell-free, circulating tumor DNA (ctDNA) isolated from blood plasma has been shown to contain genetic mutations representative of those found in the primary tumor tissue DNA (tDNA), and these samples can readily be obtained using non-invasive techniques. However, there are still no standardized methods to identify mutations in ctDNA. In the current study, we used a targeted sequencing approach with a semi-conductor based next-generation sequencing (NGS) platform to identify gene mutations in matched tDNA and ctDNA samples from 42 advanced-stage NSCLC patients from China. We identified driver mutations in matched tDNA and ctDNA in EGFR, KRAS, PIK3CA, and TP53, with an overall concordance of 76%. In conclusion, targeted sequencing of plasma ctDNA may be a feasible option for clinical monitoring of NSCLC in the near future.
