Clinical assessment of the miR-34, miR-200, ZEB1 and SNAIL EMT regulation hub underlines the differential prognostic value of EMT miRs to drive mesenchymal transition and prognosis in resected NSCLC.
Br J Cancer
; 125(11): 1544-1551, 2021 11.
Article
en En
| MEDLINE
| ID: mdl-34642464
ABSTRACT
BACKGROUND:
Patients with non-small cell lung cancer (NSCLC) receiving curative surgery have a risk of relapse, and adjuvant treatments only translate into a 5% increase in 5-year survival. We assessed the clinical significance of epithelial-mesenchymal transition (EMT) and explored its association with the [SNAIL/miR-34][ZEB/miR-200] regulation hub to refine prognostic information.METHODS:
We validated a 7-gene EMT score using a consecutive series of 176 resected NSCLC. We quantified EMT transcription factors, microRNAs (miRs) of the miR-200, miR-34 families and miR-200 promoter hypermethylation to identify outcome predictors.RESULTS:
Most tumours presented with an EMT-hybrid state and the EMT score was not predictive of outcome. Individually, all miR-200 were inversely associated with the EMT score, but only chromosome-1 miRs, miR-200a, b, 429, were associated with disease-free survival (p = 0.08, 0.05 and 0.025) and overall survival (p = 0.013, 0.003 and 0.006). We validated these associations on The Cancer Genome Atlas data. Tumour unsupervised clustering based on miR expression identified two good prognostic groups, unrelated to the EMT score, suggesting that miR profiling may have an important clinical value.CONCLUSION:
miR-200 family members do not have similar predictive value. Core EMT-miR, regulators and not EMT itself, identify NSCLC patients with a low risk of relapse after surgery.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Carcinoma de Pulmón de Células no Pequeñas
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MicroARNs
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Homeobox 1 de Unión a la E-Box con Dedos de Zinc
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Factores de Transcripción de la Familia Snail
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Neoplasias Pulmonares
Tipo de estudio:
Prognostic_studies
Límite:
Aged
/
Humans
Idioma:
En
Revista:
Br J Cancer
Año:
2021
Tipo del documento:
Article
País de afiliación:
Francia