Circulating tumor cells and clusters as liquid biomarkers for the diagnosis and prognosis of neuroblastoma
Bibliographic record
Abstract
The clinical significance of circulating tumor cell (CTC) clusters in highly metastatic tumors hasn’t yet been revealed. Here, we demonstrated the diagnostic and prognostic value of CTC clusters in neuroblastoma (NB) which is the most prevalent childhood extracranial solid tumor. We employed cascaded filter deterministic lateral displacement microfluidic chips to enrich CTCs and CTC clusters in 64 newly diagnosed NB patients. CTCs and CTC clusters were identified by CD45-, GD2+/PHOX2B+, DAPI + immunofluorescence staining, with cells displaying characteristic neoplastic morphology. Among NB patients, 85.94% and 50.00% were positive for CTCs and CTC clusters, respectively; no CTCs or CTC clusters were detected in healthy children. Moreover, CTC and CTC cluster numbers differed significantly across different primary sites, clinical and pathologic features, and risk stratifications, while no significant differences in CTC and CTC cluster counts were observed in relation to sex, age, and MYCN gene amplification. CTCs and CTC clusters indicated metastasis and strongly correlated with minimal residual disease. Of note, CTC clusters ≥ 2.5/2 mL were closely associated with bone marrow metastasis and demonstrated significant differences in the hazard ratio of overall survival. CTCs and CTC clusters are sensitive non-invasive biomarkers for NB diagnosis and prognosis, especially the prominent role in tumor emergencies. CTC clusters closely correlate with bone marrow metastasis and represent promising indicator for the monitoring of metastasis in NB emergencies. The mechanisms of CTC cluster formation and their specific role in the metastasis cascade deserve further elucidation which may serve as targets to inhibit NB bone marrow metastasis. CTC and CTC cluster counts correlate with NB tumor site and risk stage. CTCs and CTC clusters predict metastasis and CTC clusters indicate BM metastasis. CTC and CTC cluster detection play a vital role in liquid biopsy for NB emergency. CTCs and CTC clusters demonstrate prominent significance in NB OS prognosis. Studies investigating the diagnostic and prognostic value of CTC clusters in neuroblastoma are exceedingly limited. Here the authors harnessed microfluidic chip to isolate CTCs and CTC clusters and demonstrated that CTCs and CTC clusters are sensitive indicators of metastasis and risk stratification in neuroblastoma, differ significantly across different primary sites, clinical and pathologic features, and may serve as noninvasive diagnostic and prognostic biomarkers of neuroblastoma. Notably, CTC clusters may serve as promising indicators of bone marrow metastasis when bone marrow aspiration is not feasible in neuroblastoma emergencies.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".