Circulating Tumor Cells In Neuroblastoma

Jain, Mili; Kumar, Ashutosh; Mishra, Sanjay; Verma, Nishant; Goel, Madhu Mati

doi:10.4274/tjh.2017.0199

Cited by 2 publications

(3 citation statements)

References 3 publications

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“… 32 , 33 , 34 CTC clusters were also observed in high‐risk NB. 10 , 35 Herein, in this review, we will focus on the current status of the detection and collection methods for NB CTCs. The prognostic roles of CTCs in predicting tumor risk‐stratification and overall survival (OS) reported in the previous studies are also reviewed.…”

Section: Introductionmentioning

confidence: 99%

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Circulating tumor cells in neuroblastoma: Current status and future perspectives

2022

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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.

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Section: Introductionmentioning

confidence: 99%

“…It was revealed that CTCs could be detected in about 70% of high‐risk NB patients and around 50% of stem cell harvests 32–34 . CTC clusters were also observed in high‐risk NB 10,35 . Herein, in this review, we will focus on the current status of the detection and collection methods for NB CTCs.…”

Section: Introductionmentioning

confidence: 99%

Circulating tumor cells in neuroblastoma: Current status and future perspectives

2022

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“…Using capture-based methods, CTCs expressing neurogenic markers have been isolated from blood of neuroblastoma patients and shown to correlate with relapse and bone marrow metastases ( 16 – 18 ). Yet, as neuroblastoma tumor cells are mostly larger than normal blood cells (~20μm vs ~12μm), and have been found in peripheral blood samples ( 19 ), this suggests that they may be selectively concentrated by size-based separation ( 20 ). A spiral microchannel biochip utilizing inertial microfluidics and inherent centrifugal forces for size-based separation of CTCs from blood has been successfully employed in various cancers ( 21 – 25 ).…”

Section: Introductionmentioning

confidence: 99%

Pro-metastatic and mesenchymal gene expression signatures characterize circulating tumor cells of neuroblastoma patients with bone marrow metastases and relapse

et al. 2022

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Existing marker-based methods of minimal residual disease (MRD) determination in neuroblastoma do not effectively enrich for the circulating disease cell population. Given the relative size differential of neuroblastoma tumor cells over normal hematogenous cells, we hypothesized that cell size-based separation could enrich circulating tumor cells (CTCs) from blood samples and disseminated tumor cells (DTCs) from bone marrow aspirates (BMA) of neuroblastoma patients, and that their gene expression profiles could vary dynamically with various disease states over the course of treatment. Using a spiral microfluidic chip, peripheral blood of 17 neuroblastoma patients at 3 serial treatment timepoints (diagnosis, n=17; post-chemotherapy, n=11; and relapse, n=3), and bone marrow samples at diagnosis were enriched for large intact circulating cells. Profiling the resulting enriched samples with immunohistochemistry and mRNA expression of 1490 cancer-related genes via NanoString, 13 of 17 samples contained CTCs displaying cytologic atypia, TH and PHOX2B expression and/or upregulation of cancer-associated genes. Gene signatures reflecting pro-metastatic processes and the neuroblastoma mesenchymal super-enhancer state were consistently upregulated in 7 of 13 samples, 6 of which also had metastatic high-risk disease. Expression of 8 genes associated with PI3K and GCPR signaling were significantly upregulated in CTCs of patients with bone marrow metastases versus patients without. Correspondingly, in patients with marrow metastases, differentially-expressed gene signatures reflected upregulation of immune regulation in bone marrow DTCs versus paired CTCs samples. In patients who later developed disease relapse, 5 genes involved in immune cell regulation, JAK/STAT signaling and the neuroblastoma mesenchymal super-enhancer state (OLFML2B, STAT1, ARHGDIB, STAB1, TLR2) were upregulated in serial CTC samples over their disease course, despite urinary catecholamines and bone marrow aspirates not indicating the disease recurrences. In summary, using a label-free cell size-based separation method, we enriched and characterized intact circulating cells in peripheral blood indicative of neuroblastoma CTCs, as well as their DTC counterparts in the bone marrow. Expression profiles of pro-metastatic genes in CTCs correlated with the presence of bone marrow metastases at diagnosis, while longitudinal profiling identified persistently elevated expression of genes in CTCs that may serve as novel predictive markers of hematogenous MRD in neuroblastoma patients that subsequently relapse.

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Circulating Tumor Cells In Neuroblastoma

Cited by 2 publications

References 3 publications

Circulating tumor cells in neuroblastoma: Current status and future perspectives

Circulating tumor cells in neuroblastoma: Current status and future perspectives

Pro-metastatic and mesenchymal gene expression signatures characterize circulating tumor cells of neuroblastoma patients with bone marrow metastases and relapse

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