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Oncotarget ; 7(51): 85349-85364, 2016 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-27863403

RESUMO

Treatment of advanced colorectal cancer (CRC) requires multimodal therapeutic approaches and need for monitoring tumor plasticity. Liquid biopsy biomarkers, including CTCs and ctDNA, hold promise for evaluating treatment response in real-time and guiding therapeutic modifications. From 15 patients with advanced CRC undergoing liver metastasectomy with curative intent, we collected 41 blood samples at different time points before and after surgery for CTC isolation and quantification using label-free Vortex technology. For mutational profiling, KRAS, BRAF, and PIK3CA hotspot mutations were analyzed in CTCs and ctDNA from 23 samples, nine matched liver metastases and three primary tumor samples. Mutational patterns were compared. 80% of patient blood samples were positive for CTCs, using a healthy baseline value as threshold (0.4 CTCs/mL), and 81.4% of captured cells were EpCAM+ CTCs. At least one mutation was detected in 78% of our blood samples. Among 23 matched CTC and ctDNA samples, we found a concordance of 78.2% for KRAS, 73.9% for BRAF and 91.3% for PIK3CA mutations. In several cases, CTCs exhibited a mutation that was not detected in ctDNA, and vice versa. Complementary assessment of both CTCs and ctDNA appears advantageous to assess dynamic tumor profiles.


Assuntos
Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Neoplasias Colorretais/genética , Análise Mutacional de DNA/métodos , Mutação , Células Neoplásicas Circulantes/metabolismo , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Biomarcadores Tumorais/sangue , DNA Tumoral Circulante/sangue , Classe I de Fosfatidilinositol 3-Quinases/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/patologia , Análise Mutacional de DNA/instrumentação , Predisposição Genética para Doença , Células HCT116 , Humanos , Dispositivos Lab-On-A-Chip , Técnicas Analíticas Microfluídicas , Células Neoplásicas Circulantes/patologia , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Proteínas Proto-Oncogênicas B-raf/sangue , Proteínas Proto-Oncogênicas p21(ras)/sangue , Reprodutibilidade dos Testes , Fatores de Tempo
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