2026-04-17T11:35:27Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/2151982025-12-05T10:08:00Zcom_2072_1057col_2072_478916col_2072_478917col_2072_478929

00925njm 22002777a 4500 dc Murphy, Catherine author Devis Jauregui, Laura author Struck, Ronja author Boloix, Ariadna author Gallagher, Ciara author Gavin, Cian author Cottone, Federica author Soriano, Aroa author Madden, Stephen author Roma, Josep author Segura, Miguel F. author Piskareva, Olga author 2024-09-17T08:53:14Z 2024-09-17T08:53:14Z 2024-05-29 2024-09-17T08:53:15Z 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. Metàstasi Cisplatí Resistència als medicaments Expressió gènica Metastasis Cisplatin Drug resistance Gene expression 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