Evidence map›Paper›PMID 41299660›Full record

ArticleBiomarker research2025

Identification of a miRNAs signature as potential biomarker of mesenchymal phenotype in neuroblastoma patients.

Silvia Lampis, Alessandro Paolini, Virginia Di Paolo, Angela Galardi, Salvatore Raieli, Evelina Miele, Lauriane Lemelle, Francesco Fabozzi, Annalisa Serra, Angela Mastronuzzi and 4 more

Abstract readLetter
In one paragraph

Article in Biomarker research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Silvia Lampis *Hematology/Oncology and Cell and Gene Therapy Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Alessandro Paolini *Multifactorial and Complex Phenotype Research Area, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy.
Virginia Di PaoloHematology/Oncology and Cell and Gene Therapy Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Angela GalardiHematology/Oncology and Cell and Gene Therapy Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Salvatore RaieliOncodesign SA, Dijon, 21079, France.
Evelina MieleHematology/Oncology and Cell and Gene Therapy Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Lauriane LemelleSIREDO Oncology Center (Care, Innovation and Research for Children and AYA with Cancer), PSL Research University, Institut Curie, Paris, France.
Francesco FabozziHematology/Oncology and Cell and Gene Therapy Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Annalisa SerraHematology/Oncology and Cell and Gene Therapy Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Angela MastronuzziHematology/Oncology and Cell and Gene Therapy Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Maria Antonietta De IorisHematology/Oncology and Cell and Gene Therapy Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Andrea MasottiMultifactorial and Complex Phenotype Research Area, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy. andrea.masotti@opbg.net.
Franco LocatelliHematology/Oncology and Cell and Gene Therapy Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Angela Di GiannataleHematology/Oncology and Cell and Gene Therapy Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. angela.digiannatale@opbg.net.

Funding

Fondazione AIRC per la ricerca sul cancro ETS IG20213111
6 · The paper itself

Abstract

Neuroblastoma (NB) is a heterogeneous tumor, ranging from cases with spontaneous regression (MS stage) to high risk (HR) tumors. Resistance to therapy presents a major challenge in the treatment and management of HR-NB, contributing to a poor prognosis. In these patients, the resistance to conventional treatment is also related to non-genetic features, such as the cellular plasticity. Novel studies have demonstrated the presence of two distinct cell phenotypes: adrenergic (ADRN) and mesenchymal (MES), which reflect the heterogeneity of NB. MicroRNAs (miRNAs) are small, endogenous and non-coding RNAs with the ability to regulate gene expression and may have a crucial role in controlling cell plasticity. However, the role of miRNAs in NB plasticity has not been investigated yet. We investigated miRNA signature in NB cells subtypes (MES and ADRN) and in the extracellular vesicles (EVs) released by them, to identify potential MES related biomarkers. Differentially expressed miRNAs were identified by RT-qPCR and subjected to gene ontology, KEGG pathway, and protein-protein interaction network analyses. Candidate miRNAs were validated in plasma-derived EVs from NB patients. We identified miR-199a-3p as strongly upregulated in the MES cells subtype. Moreover, its expression levels were significantly higher in primary cell lines derived from HR patients compared to low-risk (LR) ones. This was confirmed by a bioinformatics analysis in patient tissue obtained from TARGET NB dataset. Protein-protein interaction analysis uncovered a complex network, with FN1, CD44, and YAP1, identified as key genes upregulated by miR-199a-3p, all of which are closely associated with the MES phenotype. Among the miRNAs significantly upregulated in EVs derived from MES cell lines, miR-584a-5p was significantly higher in EVs isolated from plasma of HR and L/Intermediate(I)R patients compared to MS. MiR-584-5p is typically considered a tumor suppressor; to support this role miR-584a-3p resulted significantly upregulated in L/IR tumor tissue, both in the INSS and COG classifications (TARGET NB database). Our findings identified specific miRNAs as MES phenotype related biomarkers. Further studies should investigate the potential impact of miRNAs on plasticity-related pathways in order to open new therapeutic strategies.

Identifiers

PMID41299660
PMCPMC12659618

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.