• 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

Related outputs

Preprint: SARS-CoV-2 infection associated cell entry proteins ACE2, CD147, PPIA, and PPIB as potential prognostic and infection biomarkers in neuroblastoma
Brandon Bergsneider, Elise Bailey, Yusuf Ahmed, Namrata Gogineni, Derek Huntley and Ximena Montano 2024. Preprint: SARS-CoV-2 infection associated cell entry proteins ACE2, CD147, PPIA, and PPIB as potential prognostic and infection biomarkers in neuroblastoma. Authorea. https://doi.org/10.22541/au.170666000.06060674/v1

Analysis of SARS-CoV-2 infection associated cell entry proteins ACE2, CD147, PPIA, and PPIB in datasets from non SARS-CoV-2 infected neuroblastoma patients, as potential prognostic and infection biomarkers in neuroblastoma
Bergsneider, B., Bailey, E., Ahmed, Y., Gogineni, N., Huntley, D. and Montano Hernandez, X. 2021. Analysis of SARS-CoV-2 infection associated cell entry proteins ACE2, CD147, PPIA, and PPIB in datasets from non SARS-CoV-2 infected neuroblastoma patients, as potential prognostic and infection biomarkers in neuroblastoma. Biochemistry and Biophysics Reports. 27 101081. https://doi.org/10.1016/j.bbrep.2021.101081

The presence of Y674/Y675 phosphorylated NTRK1 via TP53 repression of PTPN6 expression as a potential prognostic marker in neuroblastoma
Youssef, G., Gillett, C., Rampling, D., Chagtai, T., Virasami, A., Barton, J., Edwards, D., Sebire, N., Anderson, J. and Montano, X. 2019. The presence of Y674/Y675 phosphorylated NTRK1 via TP53 repression of PTPN6 expression as a potential prognostic marker in neuroblastoma. Human Pathology. 86, pp. 182-192. https://doi.org/10.1016/j.humpath.2018.12.003

A Promyelocytic Leukemia Protein-Thrombospondin-2 Axis and the Risk of Relapse in Neuroblastoma
Dvorkina, M., Nieddu, V., Chakelam, S., Pezzolo, A., Cantilena, S., Leite, A.P., Chayka, O., Regad, T., Pistorio, A., Sementa, A.R., Virasami, A., Barton, A., Montano, X., Lechertier, T., Brindle, N., Morgenstern, D., Lebras, M., Burns, A.J., Saunders N.J., Hodivala-Dilke, K., Bagella, L., De The, H., Anderson, J., Sebire, N., Pistoia, V., Sala, A. and Salomoni, P. 2016. A Promyelocytic Leukemia Protein-Thrombospondin-2 Axis and the Risk of Relapse in Neuroblastoma. Clinical Cancer Research. 22 (13), pp. 3398-3409. https://doi.org/10.1158/1078-0432.CCR-15-2081

Phosphorylation of NTRK1 at Y674/Y675 induced by TP53-dependent repression of PTPN6 expression: a potential novel prognostic marker for breast cancer
Youssef, G., Gillett, C., Agbaje, O., Crompton, T. and Montano Hernandez, X. 2014. Phosphorylation of NTRK1 at Y674/Y675 induced by TP53-dependent repression of PTPN6 expression: a potential novel prognostic marker for breast cancer. Modern Pathology. 27, pp. 361-374 23948750. https://doi.org/10.1038/modpathol.2013.129

Repression of SHP-1 Expression by p53 leads to trkA Tyrosine Phosphorylation and Suppression of Breast Cancer Cell Proliferation
Montano, Ximena 2009. Repression of SHP-1 Expression by p53 leads to trkA Tyrosine Phosphorylation and Suppression of Breast Cancer Cell Proliferation. Oncogene. 28, pp. 3787-3800. https://doi.org/10.1038/onc.2009.143

Epidermal growth factor upregulates motility of Mat-LyLu rat prostate cancer cells partially via voltage-gated Na+ channel activity
Ding, Y., Brackenbury, W.J., Uysal Onganer, P., Montano, Ximena, Porter, L.M., Bates, L.F. and Djamgoz, M.B.A. 2008. Epidermal growth factor upregulates motility of Mat-LyLu rat prostate cancer cells partially via voltage-gated Na+ channel activity. Journal of Cellular Physiology. 215 (1), pp. 77-81. https://doi.org/10.1002/jcp.21289

Epidermal growth factor, neurotrophins and the metastatic cascade in prostate cancer
Montano, Ximena and Djamgoz, Mustafa B.A. 2004. Epidermal growth factor, neurotrophins and the metastatic cascade in prostate cancer. FEBS Letters. 571, pp. 1-3. https://doi.org/10.1016/j.febslet.2004.06.088

Analysis of trk A tyrosine kinase and p53 association
Browes, C., Rowe, J., Brown, A. and Montano, Ximena 2001. Analysis of trk A tyrosine kinase and p53 association. FEBS Letters. 497, pp. 20-25. https://doi.org/10.1016/s0014-5793(01)02429-2

Common amino acid sequence motifs in p53, 14-3-3 and Akt protein families
Montano, Ximena 2001. Common amino acid sequence motifs in p53, 14-3-3 and Akt protein families. FEBS Letters. 507 (2), pp. 237-240. https://doi.org/10.1016/S0014-5793(01)02903-9

c-abl is involved in the association of p53 and trk A
Montano, Ximena 2000. c-abl is involved in the association of p53 and trk A. Oncogene. 19, pp. 3032-3040. https://doi.org/10.1038/sj.onc.1203619

Permalink - https://westminsterresearch.westminster.ac.uk/item/w8546/a-potential-prognostic-gene-signature-associated-with-p53-dependent-ntrk1-activation-and-increased-survival-of-neuroblastoma-patients


Share this

Tweet
Email

Usage statistics

70 total views
44 total downloads
These values cover views and downloads from WestminsterResearch and are for the period from September 2nd 2018, when this repository was created.