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JCI Insight. 2018 Dec 6;3(23). pii: 97021. doi: 10.1172/jci.insight.97021.

Circulating microRNA biomarkers for metastatic disease in neuroblastoma patients.

Author information

1
Center for Medical Genetics, Department of Biomolecular Medicine, and.
2
Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium.
3
Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium.
4
Pédiatrie, Hôpital de Jolimont, Haine-Saint-Paul, Belgium.
5
Department of Pathology, Medical School, University of Valencia/CIBERONC Madrid, Spain.
6
INCLIVA Biomedical Research Institute, Valencia, Spain.
7
Laboratoire de Recherche Translationnelle, Centre Léon-Bérard, Lyon, France.
8
Department of Paediatric Oncology, Institut Curie, Paris, France.
9
Molecular Oncology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
10
Pediatric Oncology and Hematology, Charité University Medicine, Berlin, Germany.
11
German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany.
12
Genome Informatics, Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
13
Department of Pediatric Oncology, University Hospital Brno, Brno, Czech Republic.
14
Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, Tel Aviv, Israel.
15
Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, USA.
16
Department of Pediatrics, Section of Hematology-Oncology, Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
17
Pediatric Oncology and Hematology, University Children's Hospital of Cologne, Medical Faculty, and.
18
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.

Abstract

In this study, the circulating miRNome from diagnostic neuroblastoma serum was assessed for identification of noninvasive biomarkers with potential in monitoring metastatic disease. After determining the circulating neuroblastoma miRNome, 743 miRNAs were screened in 2 independent cohorts of 131 and 54 patients. Evaluation of serum miRNA variance in a model testing for tumor stage, MYCN status, age at diagnosis, and overall survival revealed tumor stage as the most significant factor impacting miRNA abundance in neuroblastoma serum. Differential abundance analysis between patients with metastatic and localized disease revealed 9 miRNAs strongly associated with metastatic stage 4 disease in both patient cohorts. Increasing levels of these miRNAs were also observed in serum from xenografted mice bearing human neuroblastoma tumors. Moreover, murine serum miRNA levels were strongly associated with tumor volume. These findings were validated in longitudinal serum samples from metastatic neuroblastoma patients, where the 9 miRNAs were associated with disease burden and treatment response.

KEYWORDS:

Genetics; Noncoding RNAs; Oncology

PMID:
30518699
PMCID:
PMC6328024
DOI:
10.1172/jci.insight.97021
[Indexed for MEDLINE]
Free PMC Article

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