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

• Published in: Cancers Vol. 16; no. 4; p. 722
• Main Authors: 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, Montano, Ximena
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.02.2024
• Subjects: Biomarkers; Breast cancer; Cancer therapies; CD147 antigen; CD9 antigen; Cell activation; Cell differentiation; Cells; Children; Chromosomes; Datasets; Diagnosis; Enzymes; Gene amplification; Gene expression; Genes; Genetic aspects; Histology; Infections; KCNQ3 protein; Kinases; Lung cancer; Medical prognosis; Metastases; Molecular modelling; Motility; Neuroblastoma; p53 Protein; Patient outcomes; Patients; Phosphorylation; Potassium channels (voltage-gated); Prognosis; Proteins; Risk groups; Severe acute respiratory syndrome coronavirus 2; Solid tumors; Therapeutic targets; Transcription activation; Tumor proteins; Tumors; Canada; United Kingdom; Taiwan; United States > US; NTRK1; neuroblastoma; gene signature; prognosis; biomarkers
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers16040722

Neuroblastoma 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 , , , , , , , , , and and low , , , / , , and 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, , / , , , , and , 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.