• Journal article

A Potential Prognostic Gene Signature Associated with p53-Dependent NTRK1 Activation and Increased Survival of Neuroblastoma Patients

Currie, David, Wong, Nicole, Zane, Isabelle, Rix, Tom, Vardakastanis, Marios, Claxton, Amelia, Ong, Karine K. V., Macmorland, William, Poivet, Arthur, Brooks, Anthony, Niola, Paola, Huntley, Derek and Montano, Ximena 2024. A Potential Prognostic Gene Signature Associated with p53-Dependent NTRK1 Activation and Increased Survival of Neuroblastoma Patients. Cancers. 16 (4) 722. https://doi.org/10.3390/cancers16040722

TitleA Potential Prognostic Gene Signature Associated with p53-Dependent NTRK1 Activation and Increased Survival of Neuroblastoma Patients
TypeJournal article
AuthorsCurrie, David, Wong, Nicole, Zane, Isabelle, Rix, Tom, Vardakastanis, Marios, Claxton, Amelia, Ong, Karine K. V., Macmorland, William, Poivet, Arthur, Brooks, Anthony, Niola, Paola, Huntley, Derek and Montano, Ximena
AbstractNeuroblastoma is the most common extracranial solid tumour in children, comprising close to 10% of childhood cancer-related deaths. We have demonstrated that activation of NTRK1 by TP53 repression of PTPN6 expression is significantly associated with favourable survival in neuroblastoma. The molecular mechanisms by which this activation elicits cell molecular changes need to be determined. This is critical to identify dependable biomarkers for the early detection and prognosis of tumours, and for the development of personalised treatment. In this investigation we have identified and validated a gene signature for the prognosis of neuroblastoma using genes differentially expressed upon activation of the NTRK1-PTPN6-TP53 module. A random survival forest model was used to construct a gene signature, which was then assessed across validation datasets using Kaplan–Meier analysis and ROC curves. The analysis demonstrated that high BASP1, CD9, DLG2, FNBP1, FRMD3, IL11RA, ISGF10, IQCE, KCNQ3, and TOX2, and low BSG/CD147, CCDC125, GABRB3, GNB2L1/RACK1 HAPLN4, HEBP2, and HSD17B12 expression was significantly associated with favourable patient event-free survival (EFS). The gene signature was associated with favourable tumour histology and NTRK1-PTPN6-TP53 module activation. Importantly, all genes were significantly associated with favourable EFS in an independent manner. Six of the signature genes, BSG/CD147, GNB2L1/RACK1, TXNDC5, FNPB1, B3GAT1, and IGSF10, play a role in cell differentiation. Our findings strongly suggest that the identified gene signature is a potential prognostic biomarker and therapeutic target for neuroblastoma patients and that it is associated with neuroblastoma cell differentiation through the activation of the NTRK1-PTPN6-TP53 module.
KeywordsCancer Research
Oncology
Article number722
JournalCancers
Journal citation16 (4)
ISSN2072-6694
Year2024
PublisherMDPI AG
Publisher's version
License
CC BY 4.0
File Access Level
Open (open metadata and files)
Digital Object Identifier (DOI)https://doi.org/10.3390/cancers16040722
PubMed ID38398114
Publication dates
Published online08 Feb 2024
ProjectM159-F2
FunderOlivia Hodson Cancer Charity and the Rosetrees Trust
LicenseCC BY 4.0

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