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Open AccessArticle

Post-Surgery Circulating Tumor Cells and AXL Overexpression as New Poor Prognostic Biomarkers in Resected Lung Adenocarcinoma

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Liquid Biopsy and Metastasis Research Group, GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Avenida de la Ilustración 114, 18016 Granada, Spain
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Laboratory of Genetic Identification, Legal Medicine and Toxicology Department, Faculty of Medicine, University of Granada. Av. de la Investigación, 11, 18071 Granada, Spain
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Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine. 22 S. Greene Street, Baltimore, MD 21201, USA
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Department of Thoracic Surgery, Virgen de las Nieves University Hospital, Av. de las Fuerzas Armadas, 2, 18014 Granada, Spain
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Integral Oncology Division, San Cecilio Clinical University Hospital, Calle Dr. Oloriz 16, 18012 Granada, Spain
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Authors to whom correspondence should be addressed.
Cancers 2019, 11(11), 1750; https://doi.org/10.3390/cancers11111750
Received: 11 October 2019 / Revised: 1 November 2019 / Accepted: 4 November 2019 / Published: 7 November 2019
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. View Full-Text
Keywords: NSCLC; AXL; circulating tumor cells; prognosis; EMT; adenocarcinoma; liquid biopsy; biomarkers NSCLC; AXL; circulating tumor cells; prognosis; EMT; adenocarcinoma; liquid biopsy; biomarkers
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de Miguel-Pérez, D.; Bayarri-Lara, C.I.; Ortega, F.G.; Russo, A.; Moyano Rodriguez, M.J.; Alvarez-Cubero, M.J.; Maza Serrano, E.; Lorente, J.A.; Rolfo, C.; Serrano, M.J. Post-Surgery Circulating Tumor Cells and AXL Overexpression as New Poor Prognostic Biomarkers in Resected Lung Adenocarcinoma. Cancers 2019, 11, 1750.

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