The role of β-catenin and paired-like homeobox 2B (PHOX2B) expression in neuroblastoma patients; predictive and prognostic value

El-Shazly, Samar Sami; Hassan, Noha; Abdellateif, Mona S.; Taweel, Maha A El; Abd-Elwahab, Nahed; Ebeid, Emad

doi:10.1016/j.yexmp.2019.104272

Cited by 7 publications

(6 citation statements)

References 29 publications

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“…This unique advantage makes PHOX2B superior to other biomarkers. Studies have proved that PHOX2B can promote cell proliferation and maintain the stemness of NB 22 . High levels of PHOX2B mRNA were considered as high‐risk marker with poor response to treatment 23 .…”

Section: Discussionmentioning

confidence: 99%

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Combined analysis of PHOX2B at two time points and its value for further risk stratification in high‐risk neuroblastoma

Yue

Gao

Xing

et al. 2023

Pediatric Blood & Cancer

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Background Risk stratification of high‐risk neuroblastoma (NB) is crucial for exploring treatments. This study aimed to explore the value of minimal residual disease (MRD) based on PHOX2B levels for further risk stratification in high‐risk NB. Methods The expression of PHOX2B was monitored at two time points (after two and six cycles of induction chemotherapy, TP1 and TP2, respectively) by real‐time polymerase chain reaction (RT‐PCR). The clinical characteristics between groups and survival rates were analyzed. Results The study included 151 high‐risk patients. Positive expression of PHOX2B at diagnosis was seen in 129 cases. PHOX2B was mainly expressed in patients with high lactate dehydrogenase (LDH) and neuron‐specific enolase (NSE) levels (p < .001), bone marrow metastasis (p < .001), more than three metastatic organs (p < .001), 11q23 loss of heterozygosity (LOH) (p = .007), and when more events occurred (p = .012). The 4‐year EFS rate was significantly lower in patients with positive PHOX2B expression compared to the negative group at diagnosis (32.9% ± 6.2% vs. 74.5% ± 10.1%, p = .005). We stratified the 151 patients into three MRD risk groups: low high‐risk (low‐HR), with TP1 less than 10−4 and TP2 less than 10−4; ultra‐HR, with TP1 greater than or equal to 10−2 or TP2 greater than or equal to 10−4, and others classified as intermediate‐HR. Patients in ultra‐HR had the worst survival rate compared with other two groups (p = .02). In a multivariate model, MRD risk stratification based on PHOX2B levels at TP1 and TP2 was an independent prognostic factor for high‐risk patients (p = .001). Patients in ultra‐HR were associated with 11q23 LOH (p < .001), more than three organs of metastasis (p = .005), bone marrow metastasis (p < .001), and occurrence of more events (p = .009). Conclusions MRD risk stratification based on PHOX2B levels at two time points (after two and six cycles of induction chemotherapy) provided a stratification system for high‐risk NB, which successfully predicted treatment outcomes. Our results present an effective method for further stratification of high‐risk NB.

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Section: Discussionmentioning

confidence: 99%

“…Studies have proved that PHOX2B can promote cell proliferation and maintain the stemness of NB. 22 High levels of PHOX2B mRNA were considered as high-risk marker with poor response to treatment. 23 Until now, there was no clear definition of ultra-HR NB.…”

Section: Stutterheim Et Al Have Confirmed That Phox2b Only Expresses Inmentioning

confidence: 99%

Combined analysis of PHOX2B at two time points and its value for further risk stratification in high‐risk neuroblastoma

Yue

Gao

Xing

et al. 2023

Pediatric Blood & Cancer

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“…Наиболее часто встречаемой формой аберраций PHOX2B является расширение полиаланинового повтора (90% случаев). Нуклеотидные Строение рецептора ALK (А), варианты генетических изменений в гене ALK (Б), позиции точечных мутаций (В), сигнальные пути, запускаемые рецептором ALK (Г) [22] Figure 1 The structure of the ALK receptor (А), types of genetic alterations in the ALK gene (Б), the positions of point mutations (В), the signaling pathways activated by the ALK receptor (Г) [22] А В Б Г замены, нонсенс-мутации и сдвиг рамки считывания наблюдаются значительно реже (10%) и в единичных случаях встречаются делеции PHOX2B [9,25]. Мутации в гене PHOX2B приводят к снижению функциональной активности одноименного транскрипционного фактора [3,9], как следствие, происходит нарушение дифференцировки клеток-предшественников, а также повышение активности ALK, так как PHOX2B, предположительно, в норме ингибирует ALK [5].…”

Section: Phox2bunclassified

“…делеция PHOX2B ассоциировалась с мутациями в NF1 и амплификацией дистального участка 17q [26], кодирующего ряд протоонкогенов (анти апоптотический белок BIRC5 -survivin, транскрипционный фактор TBX2) [27,28]. В настоящее время не имеется достоверных данных о взаимосвязи аберраций PHOX2B с общепризнанными прогностическими факторами НБ [9,25].…”

Section: Phox2bunclassified

Key genetic disorders in the pathogenesis of neuroblastoma

Chernysheva

Druy

Kachanov

et al. 2021

Voprosy gematologii/onkologii i immunopatologii v pediatrii

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Neuroblastoma (NB) is a malignant neoplasm of the sympathetic nervous system of embryonic origin, consisting of undifferentiated neuroectodermal cells of the neural crest.In the structure of the incidence of malignant neoplasms in patients under one year of age, NB is the most common tumor. At the same time, mortality of this disease ranks third, behind leukemias and tumors of the central nervous system, and amounts to 13% in the structure of child mortalityfrom malignant tumors in developed countries. The stratification of patients to the risk groups and the subsequent determination of treatment tactics depends on several prognostic factors, including genetic aberrations identified in tumor cells. Moreover, processes such as spontaneous regression and transformation into benign tumors are due to the genetic characteristics of NB. Thus, the study of genetic disorders underlying the pathogenesis of NB is necessary for adequate subdivision of patients into risk groups and developing of new methods of treatment.

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“…From the viewpoint of patient prognosis, the association of subsets of these TFs with NB risk groups, patient survival, prognostic and diagnostic indications in NB has been investigated [13,[19][20][21][22][23][24][25][26], although not extensively for all of the TFs. Furthermore, many of these CRC TFs may be implicated in gene regulatory networks, molecular pathways, and signalling cascades common to various cancers.…”

Section: Introductionmentioning

confidence: 99%

Deep analysis of neuroblastoma core regulatory circuitries using online databases and integrated bioinformatics shows their pan-cancer roles as prognostic predictors

et al. 2021

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Aim Neuroblastoma is a heterogeneous childhood cancer derived from the neural crest. The dual cell identities of neuroblastoma include Mesenchymal (MES) and Adrenergic (ADRN). These identities are conferred by a small set of tightly-regulated transcription factors (TFs) binding super enhancers, collectively forming core regulatory circuitries (CRCs). The purpose of this study was to gain a deep understanding of the role of MES and ADRN TFs in neuroblastoma and other cancers as potential indicators of disease prognosis, progression, and relapse. Methods To that end, we first investigated the expression and mutational profile of MES and ADRN TFs in neuroblastoma. Moreover, we established their correlation with neuroblastoma risk groups and overall survival while establishing their extended networks with long non-coding RNAs (lncRNAs). Furthermore, we analysed the pan-cancer expression and mutational profile of these TFs and their correlation with patient survival and finally their network connectivity, using a panel of bioinformatic tools including GEPIA2, human pathology atlas, TIMER2, Omicsnet, and Cytoscape. Results We show the association of multiple MES and ADRN TFs with neuroblastoma risk groups and overall survival and find significantly higher expression of various MES and ADRN TFs compared to normal tissues and their association with overall survival and disease-free survival in multiple cancers. Moreover, we report the strong correlation of the expression of these TFs with the infiltration of stromal and immune cells in the tumour microenvironment and with stemness and metastasis-related genes. Furthermore, we reveal extended pan-cancer networks comprising these TFs that influence the tumour microenvironment and metastasis and may be useful indicators of cancer prognosis and patient survival. Conclusion Our meta-analysis shows the significance of MES and ADRN TFs as indicators of patient prognosis and the putative utility of these TFs as potential novel biomarkers.

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The role of β-catenin and paired-like homeobox 2B (PHOX2B) expression in neuroblastoma patients; predictive and prognostic value

Cited by 7 publications

References 29 publications

Combined analysis of PHOX2B at two time points and its value for further risk stratification in high‐risk neuroblastoma

Combined analysis of PHOX2B at two time points and its value for further risk stratification in high‐risk neuroblastoma

Key genetic disorders in the pathogenesis of neuroblastoma

Deep analysis of neuroblastoma core regulatory circuitries using online databases and integrated bioinformatics shows their pan-cancer roles as prognostic predictors

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