Identification of novel prognostic markers of survival time in high-risk neuroblastoma using gene expression profiles

Giwa, Abdulazeez; Fatai, Azeez Ayomide; Gamieldien, Junaid; Christoffels, Alan; Bendou, Hocine

doi:10.18632/oncotarget.27808

Cited by 9 publications

(6 citation statements)

References 81 publications

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“…Upregulation of RTL1 confers selective growth advantage in hepatocarcinoma 69 and promotes cell proliferation by regulating Wnt/β-Catenin signaling in melanoma 70 . RTL1 was one of 16 genes informative for survival time in a previous study of high-risk neuroblastomas, with stronger RTL1 expression associated with shorter survival 71 . Our linear model revealed only a minor contribution of SCNAs and germline variants to ASE in RTL1 (S.Fig.…”

Section: Resultsmentioning

confidence: 93%

Copy-number dosage regulates telomere maintenance and disease-associated pathways in neuroblastoma

Burkert

Blanc

Thiessen

et al. 2022

Preprint

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Telomere maintenance in neuroblastoma is linked to poor outcome and caused by either TERT activation or through alternative lengthening of telomeres (ALT). In contrast to TERT activation, commonly caused by genomic rearrangements or MYCN amplification, ALT is less well understood. Alterations at the ATRX locus are key drivers of ALT but only present in ~50% of ALT tumors. To identify potential new pathways to telomere maintenance, we investigate allele-specific gene dosage effects from whole genomes and transcriptomes in 115 primary neuroblastomas. We show that copy-number dosage deregulates telomere maintenance, genomic stability, and neuronal pathways and identify upregulation of variants of histone H3 and H2A as a potential alternative pathway to ALT. We investigate the interplay between TERT activation, overexpression and copy-number dosage and reveal loss of imprinting at the RTL1 gene associated with poor clinical outcome. These results highlight the importance of gene dosage in key oncogenic mechanisms in neuroblastoma.

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Section: Resultsmentioning

confidence: 93%

Copy-number dosage regulates telomere maintenance and disease-associated pathways in neuroblastoma

Burkert

Blanc

Thiessen

et al. 2022

Preprint

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“…In total, 40 genes linked to survival prediction for high-risk groups were differentially expressed between short and long-survival groups and included HOXD10 , NHLH2 , and EVX2 . Further, the ML methods used to classify high-risk patients based on the test dataset (GSE49711) for SVM and ANN models were 79% and 82% accurate, respectively [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

“…ML can be used at the interface of microbiome and genetic risk and can improve diagnosis and prognosis in NB and support more effective risk stratification. In conclusion, ML (DL/DNN, SVM, and ANN) could be used for the better stratification of high-risk patients with divergent survival patterns [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

Predicting Neuroblastoma Patient Risk Groups, Outcomes, and Treatment Response Using Machine Learning Methods: A Review

Jahangiri

2024

Medical Sciences

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Neuroblastoma, a paediatric malignancy with high rates of cancer-related morbidity and mortality, is of significant interest to the field of paediatric cancers. High-risk NB tumours are usually metastatic and result in survival rates of less than 50%. Machine learning approaches have been applied to various neuroblastoma patient data to retrieve relevant clinical and biological information and develop predictive models. Given this background, this study will catalogue and summarise the literature that has used machine learning and statistical methods to analyse data such as multi-omics, histological sections, and medical images to make clinical predictions. Furthermore, the question will be turned on its head, and the use of machine learning to accurately stratify NB patients by risk groups and to predict outcomes, including survival and treatment response, will be summarised. Overall, this study aims to catalogue and summarise the important work conducted to date on the subject of expression-based predictor models and machine learning in neuroblastoma for risk stratification and patient outcomes including survival, and treatment response which may assist and direct future diagnostic and therapeutic efforts.

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“…With the advance in the development of research techniques in life science, genetic and molecular biomarkers have been frequently examined for risk stratification and prognosis prediction in NB. For instance, the outcome of NB patients has been revealed to be associated with varying molecular signatures, including genetic mutations of specific genes ( 48 ), the methylation status of RB1 and TDGF1 ( 49 ), detectable circulating tumor DNAs in blood biopsy ( 50 ), and altered mRNA expression levels of specific gene lists ( 51 – 54 ). In this study, it was found that 542 mitochondria-related protein-encoding genes were associated with the elevated HR of NB patients, which reduced the OS with higher mRNA levels.…”

Section: Discussionmentioning

confidence: 99%

Mitochondria-associated gene expression perturbation predicts clinical outcomes and shows potential for targeted therapy in neuroblastoma

et al. 2023

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BackgroundMitochondria have long been considered a potential target in cancer therapy because malignant cells are known for their altered energy production. However, there is a lack of comprehensive research on the involvement of mitochondria-associated proteins (MAPs) in neuroblastoma (NB), and their potential as therapeutic targets is yet to be fully explored.MethodsMAP genes were defined based on the protein-coding genes with mitochondrial localization. The mRNA expression patterns and dynamics of MAP genes associated with NB were investigated by integrating publicly available transcriptional profiles at the cellular and tissue levels. Multivariate Cox regression analysis was conducted to reveal the association of MAP genes with the overall survival (OS) and clinical subgroups of NB patients. The single-cell RNA-seq dataset and gene dependency screening datasets were analyzed to reveal the therapeutic potential of targeting MAP genes.ResultsWe compiled a total of 1,712 MAP genes. We found the global and cell type-specific mRNA expression changes of the MAP genes associated with NB status and survival. Our analyses revealed a group of MAP gene signatures independent of MYCN-amplification status associated with NB outcome. We provided computational evidence with selected MAP genes showing good performance in predicting long-term prognosis. By analyzing gene dependency of the MAP genes in NB cell lines and ex vivo human primary T cells, we demonstrated the therapeutic potential of targeting several MAP genes in NB tumors.ConclusionsCollectively, our study provides evidence for the MAP genes as extended candidates in NB tumor stratification and staging, prognostic prediction, and targeted drug development.

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Identification of novel prognostic markers of survival time in high-risk neuroblastoma using gene expression profiles

Cited by 9 publications

References 81 publications

Copy-number dosage regulates telomere maintenance and disease-associated pathways in neuroblastoma

Copy-number dosage regulates telomere maintenance and disease-associated pathways in neuroblastoma

Predicting Neuroblastoma Patient Risk Groups, Outcomes, and Treatment Response Using Machine Learning Methods: A Review

Mitochondria-associated gene expression perturbation predicts clinical outcomes and shows potential for targeted therapy in neuroblastoma

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