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Int J Mol Sci ; 17(11)2016 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-27827952

RESUMO

Circulating tumor cells (CTCs) have been implicated in tumor progression and prognosis. Techniques detecting CTCs in the peripheral blood of patients with non-small cell lung carcinoma (NSCLC) may help to identify individuals likely to benefit from early systemic treatment. However, the detection of CTCs with a single marker is challenging, owing to low specificity and sensitivity and due to the heterogeneity and rareness of CTCs. Herein, the probability of cell-free RNA content in the peripheral blood as a potential biomarker for detecting CTCs in cancer patients was investigated. An immunomagnetic enrichment of real-time reverse-transcription PCR (RT-PCR) technology for analysis of CTCs in NSCLC patients was also developed. The mRNA levels of four candidate genes, cytokeratin 7 (CK7), E74-like factor 3 (ELF3), epidermal growth factor receptor (EGFR), and erythropoietin-producing hepatocellular carcinoma receptor B4 (EphB4) that were significantly elevated in tumor tissues and peripheral blood mononuclear cells (PBMCs) were determined. The expression of CK7 and ELF3 in tumor tissues and EGFR in PBMCs was associated with lymph node metastasis (all p < 0.05). The expression of CK7 in PBMCs was correlated with age and EphB4 in PBMCs correlated with histopathological type, respectively (all p < 0.05). The expression of all four genes in tumor tissues and PBMCs was significantly correlated with the clinical stage (all p < 0.01). Survival analysis showed that the patients with enhanced expression of CK7, ELF3, EGFR, and EphB4 mRNA in PBMCs had poorer disease-free survival (DFS) and overall survival (OS) than those without (all p < 0.0001). The present study showed that this alteration of cell-free RNA content in peripheral blood might have clinical ramifications in the diagnosis and treatment of NSCLC patients.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Proteínas de Ligação a DNA/genética , Receptores ErbB/genética , Queratina-7/genética , Neoplasias Pulmonares/diagnóstico , Proteínas Proto-Oncogênicas c-ets/genética , RNA Neoplásico/genética , Receptor EphB4/genética , Fatores de Transcrição/genética , Adulto , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Proteínas de Ligação a DNA/sangue , Receptores ErbB/sangue , Feminino , Humanos , Separação Imunomagnética/métodos , Queratina-7/sangue , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Prognóstico , Proteínas Proto-Oncogênicas c-ets/sangue , RNA Mensageiro/sangue , RNA Mensageiro/genética , RNA Neoplásico/sangue , Reação em Cadeia da Polimerase em Tempo Real/métodos , Receptor EphB4/sangue , Análise de Sobrevida , Fatores de Transcrição/sangue
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