MAPT (Tau) expression is a biomarker for an increased rate of survival in pediatric neuroblastoma

Zaman, Saif; Chobrutskiy, Boris I.; Blanck, George

doi:10.1080/15384101.2018.1542898

Cited by 20 publications

(23 citation statements)

References 36 publications

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“…Both genes are associated with neurodegenerative diseases, and in neuroblastoma, ectopic expression of ATXN2 sensitizes MYCN expressing cells to apoptosis [83]. Tau protein (MAPT) was not significant in any of our analyses, although one report found that Tau expression in neuroblastoma correlated with increased overall survival in neuroblastoma [84]. Tau is also a well-reported RBP in neurodegenerative diseases.…”

Section: Rbps Associated With Lower-risk Groupings and Involved In Nementioning

confidence: 58%

Identification of RNA-Binding Proteins as Targetable Putative Oncogenes in Neuroblastoma

Bell

Hagemann

Holien

et al. 2020

IJMS

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Neuroblastoma is a common childhood cancer with almost a third of those affected still dying, thus new therapeutic strategies need to be explored. Current experimental therapies focus mostly on inhibiting oncogenic transcription factor signalling. Although LIN28B, DICER and other RNA-binding proteins (RBPs) have reported roles in neuroblastoma development and patient outcome, the role of RBPs in neuroblastoma is relatively unstudied. In order to elucidate novel RBPs involved in MYCN-amplified and other high-risk neuroblastoma subtypes, we performed differential mRNA expression analysis of RBPs in a large primary tumour cohort (n = 498). Additionally, we found via Kaplan–Meier scanning analysis that 685 of the 1483 tested RBPs have prognostic value in neuroblastoma. For the top putative oncogenic candidates, we analysed their expression in neuroblastoma cell lines, as well as summarised their characteristics and existence of chemical inhibitors. Moreover, to help explain their association with neuroblastoma subtypes, we reviewed candidate RBPs’ potential as biomarkers, and their mechanistic roles in neuronal and cancer contexts. We found several highly significant RBPs including RPL22L1, RNASEH2A, PTRH2, MRPL11 and AFF2, which remain uncharacterised in neuroblastoma. Although not all RBPs appear suitable for drug design, or carry prognostic significance, we show that several RBPs have strong rationale for inhibition and mechanistic studies, representing an alternative, but nonetheless promising therapeutic strategy in neuroblastoma treatment.

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Section: Rbps Associated With Lower-risk Groupings and Involved In Nementioning

confidence: 58%

Identification of RNA-Binding Proteins as Targetable Putative Oncogenes in Neuroblastoma

Bell

Hagemann

Holien

et al. 2020

IJMS

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“…Consistent with these data, in the TAU mRNA-top quintile group, transcriptional activity was higher for proapoptotic genes and lower for proliferation-associated genes. A similar analytical approach in pediatric neuroblastoma also revealed a better prognosis for the top quintile according to the MAPT transcript analyzed on microarray (NCBO BioPortal) [112]. Again, the data were substantiated with a significant correlation with apoptotic-and proliferation-linked genes.…”

Section: Tau and Cancermentioning

confidence: 79%

“…Again, the data were substantiated with a significant correlation with apoptotic-and proliferation-linked genes. In contrast, increased survival was not associated to the mRNA for alpha-synuclein, another neurodegeneration-associated protein [112]. Evidence that transcription alterations for genes associated with neurodegenerationwith the exception of MAPT -are not common drivers of gliomas was confirmed in another study, suggesting an important role of TAU in slowing down or preventing the clinical evolution of these tumors [113].…”

Section: Tau and Cancermentioning

confidence: 96%

Tau: At the Interface Between Neurodegeneration and Cancer?

Papin¹,

Paganetti²

2020

Preprint

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For its microtubule-binding properties, the expression level of the neurodegeneration-associated protein Tau is pondered as a potential modifier of cancer resistance to chemotherapy since decades. Indeed, Tau binds microtubules at the same site as taxanes, a class of chemotherapeutic drugs designed to stabilize the microtubule network in order to stall cell division and to induce tumor cell death. Whilst independent studies report the association between low Tau expression and superior taxane response, the data were refused by a meta-analysis, suggesting interference of other parameters. Unpredictably, Tau expression level was identified as a prognostic cancer marker, whereby its positive or negative predictive value for survival depended on the cancer type. With recent experimental evidence linking Tau to P53 signaling, DNA stability and protection and to the implication of Tau in cancer is strengthened. The identification of a role of Tau at the interface between two major aging-related disorder families, neurodegeneration and cancer, offers clues for the epidemiological observation inversely correlating these disorders. Elucidating how Tau is mechanistically implicated in cellular pathways common to these devastating illnesses may extend the Tau-targeting therapeutic opportunities to cancer.

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“…MAPT is a gene encoding Tau protein, which is implicated in the pathogenesis of a number of neurodegenerative disorders, including Parkinson's disease, Alzheimer's disease, and progressive supranuclear palsy [26]. Recent studies have suggested that high MAPT expression predicts better survival outcomes in pediatric neuroblastoma, low-grade glioma, breast cancer and clear renal cell cancer [27][28][29]. Additionally, Wang et al reported that MAPT-hypermethylated tumors are associated with poor prognosis in patients with colorectal cancer [30].…”

Section: Discussionmentioning

confidence: 99%

Network-based Approach to Identify Prognosis-related Genes in Tamoxifen-treated Patients With Estrogen Receptor-positive Breast Cancer

Wang

Gong

Zhang

2020

Preprint

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Abstract Background: The estrogen receptor (ER) antagonist tamoxifen is the most commonly used endocrine therapy for ER-positive breast cancer. However, tamoxifen resistance remains a major cause of cancer recurrence and progression. Here, we aimed to identify hub genes involved in the progression and prognosis of ER-positive breast cancer following tamoxifen treatment.Results: Microarray data (GSE9838) for 155 tamoxifen-treated primary ER-positive breast cancer samples were obtained from the Gene Expression Omnibus database. In total, 1706 differentially expressed genes (DEGs) associated with tamoxifen resistance, including 859 upregulated genes and 847 downregulated genes, were identified. These DEGs were mainly enriched in functions such as protein targeting to the ER and pathways such as ribosome and oxidative phosphorylation.Weighted correlation network analysis (WGCNA) clustered genes into 13 modules, among which the tan and blue modules were the most significantly related to prognosis. From these two modules, we further identified three prognosis-related hub genes (GRSF1, MAPT, and REC8) via survival analysis. High expression ofGRSF1 predicted poor prognosis, whereas MAPT andREC8indicated favorable survival outcomes in all patients with breast cancer and in patients with ER-positive breast cancer based on The Cancer Genome Atlas database. These hub genes were further verified by reverse transcription quantitative polymerase chain reaction.Conclusion: Our findings established novel prognostic biomarkers to predict tamoxifen sensitivity, which may facilitate individualized management of breast cancer.

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MAPT (Tau) expression is a biomarker for an increased rate of survival in pediatric neuroblastoma

Cited by 20 publications

References 36 publications

Identification of RNA-Binding Proteins as Targetable Putative Oncogenes in Neuroblastoma

Identification of RNA-Binding Proteins as Targetable Putative Oncogenes in Neuroblastoma

Tau: At the Interface Between Neurodegeneration and Cancer?

Network-based Approach to Identify Prognosis-related Genes in Tamoxifen-treated Patients With Estrogen Receptor-positive Breast Cancer

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