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Updated: Aug 9, 2025
Identification of OTX1 and OTX2 As Two Possible Molecular Markers for Sinonasal Carcinomas and Olfactory Neuroblastomas
Published on: February 28, 2019
Combined analysis of PHOX2B at two time points and its value for further risk stratification in high-risk
Zhixia Yue1,2,3,4, Chao Gao1,2,3,4, Tianyu Xing1,2,3,4
1Hematologic Disease Laboratory, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing, China.
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.
