In:
PLOS ONE, Public Library of Science (PLoS), Vol. 19, No. 5 ( 2024-5-29), p. e0303643-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0303643
DOI:
10.1371/journal.pone.0303643.g001
DOI:
10.1371/journal.pone.0303643.g002
DOI:
10.1371/journal.pone.0303643.g003
DOI:
10.1371/journal.pone.0303643.g004
DOI:
10.1371/journal.pone.0303643.g005
DOI:
10.1371/journal.pone.0303643.g006
DOI:
10.1371/journal.pone.0303643.g007
DOI:
10.1371/journal.pone.0303643.s001
DOI:
10.1371/journal.pone.0303643.s002
DOI:
10.1371/journal.pone.0303643.s003
DOI:
10.1371/journal.pone.0303643.s004
DOI:
10.1371/journal.pone.0303643.s005
DOI:
10.1371/journal.pone.0303643.s006
DOI:
10.1371/journal.pone.0303643.s007
DOI:
10.1371/journal.pone.0303643.s008
DOI:
10.1371/journal.pone.0303643.s009
DOI:
10.1371/journal.pone.0303643.s010
DOI:
10.1371/journal.pone.0303643.s011
DOI:
10.1371/journal.pone.0303643.r001
DOI:
10.1371/journal.pone.0303643.r002
DOI:
10.1371/journal.pone.0303643.r003
DOI:
10.1371/journal.pone.0303643.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2024
detail.hit.zdb_id:
2267670-3
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