Bone marrow aspirate Cit-H3 was identified as a novel biomarker of minimal residual disease in neuroblastoma.

BACKGROUND

Neuroblastoma (NB) is the most prevalent extracranial solid tumor in children. Neutrophils release neutrophil extracellular traps (NETs) following intense or prolonged activation. Neutrophil elastase (ELA2) and citrullinated histone H3 (Cit-H3) are specific markers of NETs. Additionally, neuron-specific enolase (NSE) serves as a biomarker and can be used to monitor the condition of NB progression, assess treatment response, and predict recurrence.

METHODS

This study employed a retrospective study design, and all samples were collected prior to bone marrow aspiration for diagnosis. A total of 39 serum samples from patients diagnosed with NB by postoperative pathological bone marrow aspiration were included as the study subjects, and neutrophils, ELA2, and Cit-H3 were detected in the study subjects using ELISA. The blood routine data of 99 patients diagnosed with NB were collected, and these data were from patients different from those of the aforementioned 39 serum samples. And patients were divided into two groups, namely NB patients with positive bone marrow metastasis and those without metastasis, based on the result of bone marrow GD2 immunohistochemical staining. All data were statistically analyzed using IBM SPSS Statistics 26.0 and GraphPad Prism 9.0 software.

RESULTS

A positive correlation was identified between NB bone marrow minimal residual disease (MRD) positivity and haematological indices, including interleukin-2 (IL-2) (p = 0.021), IL-6 (p = 0.030), NSE (p < 0.001), and Cit-H3 (p < 0.001). And MRD was positively associated with blood neutrophils in bone marrow (p < 0.05).

CONCLUSIONS

This study demonstrates a significant correlation between NETs and MRDs, and found a positive correlation between bone marrow MRD+ and the indicators of IL-2, IL-6, and NSE, as well as a positive correlation with bone marrow neutrophils. And Cit-H3 was identified as a new biomarker and found a positive correlation between Cit-H3 and bone marrow MRD+.