The pathogenesis of neuroblastoma with bone or bone marrow metastasis (NB-BBM) and its complex immune microenvironment remain poorly elucidated, hampering the advancement of effective risk prediction for BBM and limiting therapeutic strategies. Feature recognition of 142 paraffin-embedded hematoxylin-eosin-stained tumor section images was conducted using a Swin-Transformer for pathological histology to predict NB-BBM occurrence. Single-cell transcriptomics identified a tumor cell subpopulation (NB3) and two tumor-associated macrophage (TAM) subpopulations (SPP1 TAMs and IGHM TAMs) closely associated with BBM and highlighted transketolase (TKT) as a key molecular marker for metastatic progression in NB. This extensive multi-omics investigation into NB-BBM enhances our understanding of single-cell transcriptional dynamics in NB beyond existing research, outlining the evolution from carcinoma through tumorigenesis to bone marrow metastases. Furthermore, exploration of the immune microenvironment identified specific subpopulations of TAMs crucial in promoting NB-BBM, presenting new avenues for immunotherapy. These insights enhance our understanding of the metastatic process from NB to BBM and facilitate the development of more effective diagnostic and therapeutic strategies for this aggressive pediatric cancer.
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| http://dx.doi.org/10.1016/j.gendis.2024.101511 | DOI Listing |
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