Royal College of Surgeons in Ireland
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In vivo cisplatin-resistant neuroblastoma metastatic model reveals tumour necrosis factor receptor superfamily member 4 (TNFRSF4) as an independent prognostic factor of survival in neuroblastoma

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posted on 2024-10-24, 09:01 authored by Catherine Murphy, Laura Devis-Jauregui, Ronja StruckRonja Struck, Ariadna Boloix, Ciara GallagherCiara Gallagher, Cian Gavin, Federica CottoneFederica Cottone, Aroa Soriano Fernandez, Stephen MaddenStephen Madden, Josep Roma, Miguel F Segura, Olga PiskarevaOlga Piskareva

Neuroblastoma is the most common solid extracranial tumour in children. Despite major advances in available therapies, children with drug-resistant and/or recurrent neuroblastoma have a dismal outlook with 5-year survival rates of less than 20%. Therefore, tackling relapsed tumour biology by developing and characterising clinically relevant models is a priority in finding targetable vulnerability in neuroblastoma. Using matched cisplatin-sensitive KellyLuc and resistant KellyCis83Luc cell lines, we developed a cisplatin-resistant metastatic MYCN-amplified neuroblastoma model. The average number of metastases per mouse was significantly higher in the KellyCis83Luc group than in the KellyLuc group. The vast majority of sites were confirmed as having lymph node metastasis. Their stiffness characteristics of lymph node metastasis values were within the range reported for the patient samples. Targeted transcriptomic profiling of immuno-oncology genes identified tumour necrosis factor receptor superfamily member 4 (TNFRSF4) as a significantly dysregulated MYCN-independent gene. Importantly, differential TNFRSF4 expression was identified in tumour cells rather than lymphocytes. Low TNFRSF4 expression correlated with poor prognostic indicators in neuroblastoma, such as age at diagnosis, stage, and risk stratification and significantly associated with reduced probability of both event-free and overall survival in neuroblastoma. Therefore, TNFRSF4 Low expression is an independent prognostic factor of survival in neuroblastoma. 

Funding

Neuroblastoma UK

RCSI Strategic Academic Recruitment (StAR) Programme

Health Research Board - The Conor Foley Neuroblastoma Cancer Research Foundation (HRCI-HRB-2022-013)

Irish Research Council Postgraduate Programme (GOIPG/2019/3220)

Irish Research Council - The Conor Foley Neuroblastoma Cancer Research Foundation (EPSPG/2021/95)

Instituto de Salud Carlos III through the projects “ICI21/00076”, “PI23/01144” and “PMP21/00073” (Co-funded by the European Regional Development Fund/European Social Fund; “A way to make Europe”/ “Investing in your future”)

Ramón y Cajal scheme (Grant No. RyC-2021-034346-I)

Spanish Ministry for Science and Innovation (MCIN)

TITLE: Phase I trial of ABTL0812 in children with relapsed or refractory neuroblastoma and extra-cranial solid tumors

Instituto de Salud Carlos III

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SEHOP-PENCIL - National strategy for the implementation of personalized medicine in children and adolescents with cancer

Instituto de Salud Carlos III

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History

Data Availability Statement

Data is contained within the article or Supporting Information material. RNA sequencing data “NeuroblastomaKellyLuc-Kelly83Luc xenografts, the HTG EdgeSeq immuno-oncology panel” is deposited at R2:Genomics Analysis and Visualization Platform (http://r2.amc.nl; ID: Xenograft Neuroblastoma KellyLuc (Immuno-oncology panel) - Piskareva-10 - custom - rsg001

Comments

The original article is available at https://journals.plos.org/

Published Citation

Murphy C. et al. In vivo cisplatin-resistant neuroblastoma metastatic model reveals tumour necrosis factor receptor superfamily member 4 (TNFRSF4) as an independent prognostic factor of survival in neuroblastoma. PLoS One. 2024;19(5):e0303643.

Publication Date

29 May 2024

PubMed ID

38809883

Department/Unit

  • Amber (Advanced Material & Bioengineering Research) Centre
  • Anatomy and Regenerative Medicine
  • Data Science Centre
  • School of Pharmacy and Biomolecular Sciences
  • School of Population Health
  • Tissue Engineering Research Group (TERG)

Publisher

Public Library of Science

Version

  • Published Version (Version of Record)