Extracellular vesicles miR-574-5p and miR-181a-5p as prognostic markers in NSCLC patients treated with nivolumab.
Humans
MicroRNAs
/ genetics
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Male
Female
Middle Aged
Prognosis
Aged
Nivolumab
/ therapeutic use
Lung Neoplasms
/ drug therapy
Biomarkers, Tumor
/ genetics
Extracellular Vesicles
/ genetics
Aged, 80 and over
Adult
Immune Checkpoint Inhibitors
/ therapeutic use
Antineoplastic Agents, Immunological
/ therapeutic use
Extracellular vesicle miRNA
Immune checkpoint inhibitor
Nivolumab
Non-small cell lung cancer (NSCLC)
Pluripotency of stem cell
Prognosis score
Toll-like receptor
miR-574-5p and miR-181a-5p
Journal
Clinical and experimental medicine
ISSN: 1591-9528
Titre abrégé: Clin Exp Med
Pays: Italy
ID NLM: 100973405
Informations de publication
Date de publication:
06 Aug 2024
06 Aug 2024
Historique:
received:
12
04
2024
accepted:
07
07
2024
medline:
6
8
2024
pubmed:
6
8
2024
entrez:
6
8
2024
Statut:
epublish
Résumé
Immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced non-small cell lung cancer (NSCLC), although patient survival is still unsatisfactory. Accurate predictive markers capable of personalizing the treatment of patients with NSCLC are still lacking. Circulating extracellular vesicles involved in cell-to-cell communications through miRNAs (EV-miRs) transfer are promising markers. Plasma from 245 patients with advanced NSCLC who received nivolumab as second-line therapy was collected and analyzed. EV-miRnome was profiled on 174/245 patients by microarray platform, and selected EV-miRs were validated by qPCR. A prognostic model combining EV-miR and clinical variables was built using stepwise Cox regression analysis and tested on an independent patient cohort (71/245). EV-PD-L1 gene copy number was assessed by digital PCR. For 54 patients with disease control, EV-miR changes at best response versus baseline were investigated by microarray and validated by qPCR. EV-miRNome profiling at baseline identified two EV-miRs (miR-181a-5p and miR-574-5p) that, combined with performance status, are capable of discriminating patients unlikely from those that are likely to benefit from immunotherapy (median overall survival of 4 months or higher than 9 months, respectively). EV-PD-L1 digital evaluation reported higher baseline copy number in patients at increased risk of mortality, without improving the prognostic score. Best response EV-miRNome profiling selected six deregulated EV-miRs (miR19a-3p, miR-20a-5p, miR-142-3p, miR-1260a, miR-1260b, and miR-5100) in responding patients. Their longitudinal monitoring highlighted a significant downmodulation already in the first treatment cycles, which lasted more than 6 months. Our results demonstrate that EV-miRs are promising prognostic markers for NSCLC patients treated with nivolumab.
Identifiants
pubmed: 39105937
doi: 10.1007/s10238-024-01427-8
pii: 10.1007/s10238-024-01427-8
doi:
Substances chimiques
MicroRNAs
0
Nivolumab
31YO63LBSN
Biomarkers, Tumor
0
MIrn181 microRNA, human
0
MIRN574 microRNA, human
0
Immune Checkpoint Inhibitors
0
Antineoplastic Agents, Immunological
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
182Subventions
Organisme : Ministero della Salute
ID : 5×1000 funds: 2018-2019
Organisme : Ministero della Salute
ID : CO-2016-02361470
Organisme : Ministero della Salute
ID : Ricerca Corrente 2022, RRC 2022
Organisme : Bristol-Myers Squibb
ID : CA209-828-BMS
Organisme : Compagnia di San Paolo
ID : 2017-0529
Informations de copyright
© 2024. The Author(s).
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