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3.
Cancers (Basel) ; 11(11)2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31703465

RESUMO

BACKGROUND: The prognosis of early stage non-small cell lung cancer (NSCLC) is quite disappointing and the benefits of adjuvant therapy are relatively small. Thus, there is an urgent need to identify novel prognostic and predictive biomarkers. Lung adenocarcinoma has distinct clinical-pathological characteristics and novel therapeutic strategies are under active evaluation in the adjuvant setting. Here, we investigated the prognostic impact of circulating tumor cells (CTCs) and gene and miRNA tissue expression in resectable NSCLC. PATIENTS AND METHODS: We assessed the association between CTC subpopulations and the outcome of resected early stage lung adenocarcinoma (ADC) patients at three different time-points (CTC1-3) (before surgery, after one month, and after six months) in comparison to squamous cell carcinoma (SCC). Furthermore, gene and miRNA tissue expression, immunoprofiling, and epithelial-to-mesenchymal transition (EMT) markers were correlated with outcome. RESULTS: ADC (n = 47) and SCC (n = 50) revealed different tissue expression profiles, resulting in the presence of different CTC subpopulations. In ADC, miR-155 correlated with AXL and IL6R expression, which were related to the presence of EMT CTC1 (p = 0.014 and p = 0.004). In the multivariate analysis, CTC2 was an independent prognostic factor for relapse-free survival, and CTC3 and AXL were independent prognostic for overall survival only in ADC. Neither the surgery nor the adjuvant treatment influenced the prognosis of these patients. CONCLUSIONS: Our study elucidate the prognostic impact of tissue AXL expression and the presence of CTCs after surgery in adenocarcinoma patients. Tissue AXL expression and CTC EMT activation could potentially represent biomarkers for the stratification of ADC patients that might benefit from new adjuvant therapies.

9.
Eur J Cardiothorac Surg ; 52(1): 55-62, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28369376

RESUMO

OBJECTIVES: More than 20% of lung cancer patients develop a recurrence, even after curative resection. We hypothesized that relapse may arise from the dissemination of circulating tumour cells (CTCs). This study evaluates the significance of CTC detection as regards the recurrence of non-small-cell lung cancer (NSCLC) in surgically resected patients. Secondly, we investigated the association between CTCs and the uptake of 18 F-fluorodeoxyglucose (FDG) by the primary tumour on a positron emission tomographic (PET) scan. METHODS: In this single-centre prospective study, blood samples for analysis of CTCs were obtained from 102 patients with Stage I-IIIA NSCLC both before (CTC1) and 1 month after (CTC2) radical resection. CTCs were isolated using immunomagnetic techniques. The presence of CTCs was correlated with the maximum standardized uptake value (SUVmax) measured on preoperative FDG PET/computed tomographic scans. Recurrence free survival (RFS) analysis was performed. RESULTS: CTCs were detected in 39.2% of patients before and in 27.5% 1 month after the operation. The presence of CTCs after the operation was significantly correlated with SUVmax on PET scans, pathological stage and surgical approach. Only SUVmax was an independent predictor for the presence of CTC2 on multivariate analysis. Postoperative CTCs were significantly correlated with a shorter RFS ( P = 0.005). In multivariate analysis, the presence of CTC2 was associated with RFS, independent of disease staging. CONCLUSIONS: Detection of CTCs 1 month after radical resection might be a useful marker to predict early recurrence in Stage I-III NSCLC. The SUVmax value of the primary tumour on preoperative PET scans was associated with the presence of CTC 1 month after the operation.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Fluordesoxiglucose F18/farmacocinética , Neoplasias Pulmonares/diagnóstico , Estadiamento de Neoplasias , Células Neoplásicas Circulantes/patologia , Pneumonectomia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Idoso , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/cirurgia , Masculino , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/metabolismo , Células Neoplásicas Circulantes/metabolismo , Estudos Prospectivos , Compostos Radiofarmacêuticos/farmacocinética , Fatores de Tempo
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