Prospective investigation of applicability and the prognostic significance of bone marrow involvement in patients with neuroblastoma detected by quantitative reverse transcription PCR

Druy, Alexander; Shorikov, Egor; Tsaur, Grigory; Popov, Alexander; Zaychikov, A.; Tuponogov, S. N.; Saveliev, Leonid; Tytgat, Godelieve A.M.; Fechina, Larisa

doi:10.1002/pbc.27354

Cited by 16 publications

(25 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In our study, the patients with low/intermediate-risk group also had worse EFS and OS with PHOX2B positive expression in BM and PB samples at diagnosis than patients without it. The results of our research and Druy et al supported that patients with PHOX2B expression in BM or PB in the favorable group at diagnosis may suffer from disseminated disease and probably will benefit from upstaging therapy [9].…”

Section: Discussionsupporting

confidence: 80%

“…patients with the expression of PHOX2B/TH in BM at diagnosis in 69 patients with localized and stage 4S neuroblastoma also had unfavorable 5-year EFS and OS. Moreover, the survival rates of these patients did not differ significantly from patients with metastatic lesions [9]. In our study, the patients with low/intermediate-risk group also had worse EFS and OS with PHOX2B positive expression in BM and PB samples at diagnosis than patients without it.…”

Section: Discussioncontrasting

confidence: 44%

“…The expression of PHOX2B in BM and PB in low/intermediate-risk patients were also detected in our research. Druy et al revealed the patients with positive expression of PHOX2B/TH in BM at diagnosis had a significant adverse 5-year EFS and OS in total 93 neuroblastoma patients [9]. Unfortunately, 10…”

Section: Discussionmentioning

confidence: 99%

“…Paired-like homeobox 2B (PHOX2B) gene, located on chromosome 4p13 [7], is specifically expressed in the nervous system including neuroblastoma cells, but not in normal bone marrow or peripheral blood cells of patients [8,9]. Previously, some studies showed PHOX2B could be used as a biomarker for minimal residual disease (MRD) and predicting prognosis in neuroblastoma patients [9][10][11][12]. In our study, we evaluated the diagnostic significance of PHOX2B expression in bone marrow (BM) and peripheral blood (PB) for disseminated diseases and patients' outcomes.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

PHOX2B expression in bone marrow and peripheral blood is associated with metastasis and prognosis in patients with neuroblastoma

Fan¹,

Xing²,

Hong³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Paired-like homeobox 2B (PHOX2B) is specifically expressed in the nervous system including neuroblastoma cells, but little is known about the clinical significance of the expression of PHOX2B in bone marrow (BM) and peripheral blood (PB) samples of newly diagnosed neuroblastoma patients. Methods The expression of PHOX2B in 276 paired BM and PB samples of neuroblastoma patients at diagnosis was tested by quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Then the relationship between PHOX2B level and clinical characteristics including metastasis and prognosis was explored by receiver operating characteristic (ROC) analysis and Kaplan-Meier method. Results We identified the combined expression of PHOX2B in both BM and PB provided a high diagnostic accuracy for metastasis of neuroblastoma patients (AUC = 0.920) with the sensitivity and specificity of 86.7% and 92.9%, respectively. At last, 246 patients were enrolled for prognostic analysis. The median follow-up time was 22 months. Positive expressions of PHOX2B in BM and PB at diagnosis were associated with worse EFS and OS in neuroblastoma patients (P < 0.05). What’s worse, 19.7% (31/157) and 6.4% (10/157) patients with positive expression of PHOX2B in BM and PB samples in low/intermediate-risk group also had shorter EFS and poor OS (P < 0.05). CONCLUSIONS The expressions of PHOX2B in BM and PB were high in patients with unfavorable clinical characteristics. PHOX2B could be an appropriate biomarker for predicting metastasis and prognosis in patients with neuroblastoma.

show abstract

Section: Discussionsupporting

confidence: 80%

Section: Discussioncontrasting

confidence: 44%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

PHOX2B expression in bone marrow and peripheral blood is associated with metastasis and prognosis in patients with neuroblastoma

Fan¹,

Xing²,

Hong³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…A set of five markers (CHGA, DCX, DDC, PHOX2B, TH) normalized by four references (B2M, GAPDH, HPRT1, SDHA) was also developed (101, 126). In addition, several amended sets of two markers (DCX, TH) for BM and PB samples (95), three markers (B4GALNT1, DDC, TH) for BM and PB samples (127), four markers (B4GALNT1, CCND1, ISL1, PHOX2B) for BM sample (129, 130), and four markers (B4GALNT1, ELAVL4, PHOX2B, TH) for BM sample were reported (131).…”

Section: Mrd Detection In Neuroblastoma Patientsmentioning

confidence: 99%

Dynamics of Minimal Residual Disease in Neuroblastoma Patients

et al. 2019

View full text Add to dashboard Cite

Neuroblastoma is a common extracranial solid tumor of neural crest (NC) origin that accounts for up to 15% of all pediatric cancer deaths. The disease arises from a transient population of NC cells that undergo an epithelial-mesenchymal transition (EMT) and generate diverse cell-types and tissues. Patients with neuroblastoma are characterized by their extreme heterogeneity ranging from spontaneous regression to malignant progression. More than half of newly diagnosed patients present highly metastatic tumors and are stratified into a high-risk group with dismal outcome. As many as 20% of high-risk patients have residual disease that is refractory or progressive during induction chemotherapy. Although a majority of high-risk patients achieve remission, larger part of those patients has minimal residual disease (MRD) that causes relapse even after additional consolidation therapy. MRD is composed of drug-resistant tumor cells and dynamically presented as cancer stem cells (CSCs) in residual tumors, circulating tumor cells (CTCs) in peripheral blood (PB), and disseminated tumor cells (DTCs) in bone marrow (BM) and other metastatic sites. EMT appears to be a key mechanism for cancer cells to acquire MRD phenotypes and malignant aggressiveness. Due to the restricted availability of residual tumors, PB and BM have been used to isolate and analyze CTCs and DTCs to evaluate MRD in cancer patients. In addition, recent technical advances make it possible to use circulating tumor DNA (ctDNA) shed from tumor cells into PB for MRD evaluation. Because MRD can be detected by tumor-specific antigens, genetic or epigenetic changes, and mRNAs, numerous assays using different methods and samples have been reported to detect MRD in cancer patients. In contrast to the tumor-specific gene-rearrangement-positive acute lymphoblastic leukemia (ALL) and the oncogenic fusion-gene-positive chronic myelogenous leukemia (CML) and several solid tumors, the clinical significance of MRD remains to be established in neuroblastoma. Given the extreme heterogeneity of neuroblastoma, dynamics of MRD in neuroblastoma patients will hold a key to the clinical validation. In this review, we summarize the biology and detection methods of cancer MRD in general and evaluate the available assays and clinical significance of neuroblastoma MRD to clarify its dynamics in neuroblastoma patients.

show abstract

Circulating tumor cells in neuroblastoma: Current status and future perspectives

2022

View full text Add to dashboard Cite

Neuroblastoma is the most common extracranial solid tumor in children, accounting for 10% to 20% of deaths of pediatric malignancies. Due to the poor prognosis and significant biological heterogeneity of neuroblastoma, it is essential to develop personalized therapeutics and monitor treatment response. Circulating tumor cells (CTCs), as one of the important analytes for liquid biopsy, could facilitate response assessment and outcome prediction for patients in a non‐invasive way. Several methods and platforms have been used for the enrichment and detection of CTCs. The enumeration of CTCs counts and evaluation of tumor‐specific mRNA transcript levels could provide prognostic information at diagnosis, during or after chemotherapy, and during the process of disease progression. So far, studies into neuroblastoma CTCs are only in the preliminary stages. The quality‐controlled large prospective cohort studies are needed to evaluate the clinical significance and statistical rigor of CTC detection methods. Moreover, there remains a lot to be explored and investigated in genotyping characterization of neuroblastoma (NB) CTCs and construction of in‐vitro or in‐vivo functional models. CTCs and circulating tumor DNA (ctDNA) analysis will be complementary in understanding tumor heterogeneity and evolution over the course of therapy for patients with NB in the future.

show abstract

Prospective investigation of applicability and the prognostic significance of bone marrow involvement in patients with neuroblastoma detected by quantitative reverse transcription PCR

Abstract: PHOX2B and TH are the most optimal markers for detection of BM involvement, allowing identification of high-risk patients. Predominance of PHOX2B expression over TH has a strong adverse prognostic impact.

Cited by 16 publications

References 24 publications

PHOX2B expression in bone marrow and peripheral blood is associated with metastasis and prognosis in patients with neuroblastoma

PHOX2B expression in bone marrow and peripheral blood is associated with metastasis and prognosis in patients with neuroblastoma

Dynamics of Minimal Residual Disease in Neuroblastoma Patients

Circulating tumor cells in neuroblastoma: Current status and future perspectives

Contact Info

Product

Resources

About