High Oct4 expression: implications in the pathogenesis of neuroblastic tumours View Full Text


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Article Info

DATE

2019-01-03

AUTHORS

Ezequiel Monferrer, Rebeca Burgos-Panadero, Maite Blanquer-Maceiras, Adela Cañete, Samuel Navarro, Rosa Noguera

ABSTRACT

BACKGROUND: Neuroblastic tumours (NBTs) are paediatric solid tumours derived from embryonic neural crest cells which harbour their own cancer stem cells (CSC). There is evidence indicating that CSC may be responsible for tumour progression, chemotherapy resistance and recurrence in NBTs. Oct4 is a transcription factor which plays a key role in mammal embryonic development and stem cell fate regulation. The aim of the study is to elucidate the clinical significance of Oct4 in NBTs. METHODS: We studied Oct4 expression in 563 primary NBTs using digital image quantification. Chi-square test was applied to analyse the correlation between histopathology and the Oct4+ cell percentage. Survival analysis was carried out with Kaplan-Meier curves and log-rank test. Additionally, a multivariate Cox regression analysis with the stepwise backwards (Wald) method was undertaken to calculate the impact of Oct4 expression level on survival. RESULTS: We found that tumours with a high proportion of cells expressing Oct4 correlated statistically with undifferentiated and poorly differentiated neuroblastoma / nodular ganglioneuroblastoma, and that Oct4 expression was not present in ganglioneuroma (p < 0.05). Statistical analysis also indicated a relationship between high Oct4 expression levels, high-risk patients according to the International Neuroblastoma Risk Group pre-treatment classification parameters, larger blood vessels and low survival rates. CONCLUSIONS: These results suggest that the Oct4 gene may regulate NBT pathogenic differentiation pathways, and should thus be considered as a target for knockdown when developing novel therapies for high-risk NBT patients. More... »

PAGES

1

References to SciGraph publications

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  • 2011-03-15. Oct-4+/Tenascin C+ neuroblastoma cells serve as progenitors of tumor-derived endothelial cells in CELL RESEARCH
  • 2011-07-02. Expression analysis of stem cell-related genes reveal OCT4 as a predictor of poor clinical outcome in medulloblastoma in JOURNAL OF NEURO-ONCOLOGY
  • 2016-07-14. Extracellular matrix composition defines an ultra-high-risk group of neuroblastoma within the high-risk patient cohort in BRITISH JOURNAL OF CANCER
  • 2017-04-13. Knockdown of stem cell regulator Oct4A in ovarian cancer reveals cellular reprogramming associated with key regulators of cytoskeleton-extracellular matrix remodelling in SCIENTIFIC REPORTS
  • Identifiers

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    http://scigraph.springernature.com/pub.10.1186/s12885-018-5219-3

    DOI

    http://dx.doi.org/10.1186/s12885-018-5219-3

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    35 schema:description BACKGROUND: Neuroblastic tumours (NBTs) are paediatric solid tumours derived from embryonic neural crest cells which harbour their own cancer stem cells (CSC). There is evidence indicating that CSC may be responsible for tumour progression, chemotherapy resistance and recurrence in NBTs. Oct4 is a transcription factor which plays a key role in mammal embryonic development and stem cell fate regulation. The aim of the study is to elucidate the clinical significance of Oct4 in NBTs. METHODS: We studied Oct4 expression in 563 primary NBTs using digital image quantification. Chi-square test was applied to analyse the correlation between histopathology and the Oct4<sup>+</sup> cell percentage. Survival analysis was carried out with Kaplan-Meier curves and log-rank test. Additionally, a multivariate Cox regression analysis with the stepwise backwards (Wald) method was undertaken to calculate the impact of Oct4 expression level on survival. RESULTS: We found that tumours with a high proportion of cells expressing Oct4 correlated statistically with undifferentiated and poorly differentiated neuroblastoma / nodular ganglioneuroblastoma, and that Oct4 expression was not present in ganglioneuroma (p &lt; 0.05). Statistical analysis also indicated a relationship between high Oct4 expression levels, high-risk patients according to the International Neuroblastoma Risk Group pre-treatment classification parameters, larger blood vessels and low survival rates. CONCLUSIONS: These results suggest that the Oct4 gene may regulate NBT pathogenic differentiation pathways, and should thus be considered as a target for knockdown when developing novel therapies for high-risk NBT patients.
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    43 Group pre-treatment classification parameters
    44 International Neuroblastoma Risk Group pre-treatment classification parameters
    45 Kaplan-Meier curves
    46 Neuroblastoma Risk Group pre-treatment classification parameters
    47 OCT4 expression levels
    48 Oct4 expression
    49 Oct4 gene
    50 Risk Group pre-treatment classification parameters
    51 aim
    52 analyse
    53 analysis
    54 blood vessels
    55 cancer stem cells
    56 cell fate regulation
    57 cell percentage
    58 cells
    59 chemotherapy resistance
    60 chi-square test
    61 classification parameters
    62 clinical significance
    63 correlation
    64 crest cells
    65 curves
    66 development
    67 differentiation pathway
    68 digital image quantification
    69 embryonic development
    70 embryonic neural crest cells
    71 evidence
    72 expression
    73 expression levels
    74 factors
    75 fate regulation
    76 ganglioneuroblastoma
    77 ganglioneuroma
    78 genes
    79 high Oct4 expression levels
    80 high-risk patients
    81 higher proportion
    82 histopathology
    83 image quantification
    84 impact
    85 implications
    86 key role
    87 knockdown
    88 large blood vessels
    89 levels
    90 log-rank test
    91 lower survival rate
    92 mammal embryonic development
    93 method
    94 multivariate Cox regression analysis
    95 neural crest cells
    96 neuroblastic tumors
    97 neuroblastoma / nodular ganglioneuroblastoma
    98 nodular ganglioneuroblastoma
    99 novel therapies
    100 own cancer stem cells
    101 parameters
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    103 pathogenic differentiation pathways
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    105 patients
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    108 pre-treatment classification parameters
    109 primary neuroblastic tumors
    110 progression
    111 proportion
    112 quantification
    113 rate
    114 recurrence
    115 regression analysis
    116 regulation
    117 relationship
    118 resistance
    119 results
    120 role
    121 significance
    122 solid tumors
    123 statistical analysis
    124 stem cells
    125 stepwise
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