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.
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
25
02
2021
accepted:
24
09
2021
revised:
31
08
2021
pubmed:
14
10
2021
medline:
6
1
2022
entrez:
13
10
2021
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 34642464
doi: 10.1038/s41416-021-01568-7
pii: 10.1038/s41416-021-01568-7
pmc: PMC8609001
doi:
Substances chimiques
MIRN200 microRNA, human
0
MIRN34 microRNA, human
0
MicroRNAs
0
SNAI1 protein, human
0
Snail Family Transcription Factors
0
ZEB1 protein, human
0
Zinc Finger E-box-Binding Homeobox 1
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1544-1551Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Limited.
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