Single-cell RNA sequencing explored potential therapeutic targets by revealing the tumor microenvironment of neuroblastoma and its expression in cell death.

Background: Neuroblastoma (NB) is the most common extracranial solid tumor in childhood and is closely related to the early development and differentiation of neuroendocrine (NE) cells. The disease is mainly represented by high-risk NB, which has the characteristics of high mortality and difficult treatment. The survival rate of high-risk NB patients is not ideal. In this article, we not only conducted a comprehensive study of NB through single-cell RNA sequencing (scRNA-seq) but also further analyzed cuproptosis, a new cell death pathway, in order to find clinical treatment targets from a new perspective.

Materials And Methods: The Seurat software was employed to process the scRNA-seq data. This was followed by the utilization of GO enrichment analysis and GSEA to unveil pertinent enriched pathways. The inferCNV software package was harnessed to investigate chromosomal copy number variations. pseudotime analyses involved the use of Monocle 2, CytoTRACE, and Slingshot software. CellChat was employed to analyze the intercellular communication network for NB. Furthermore, PySCENIC was deployed to review the profile of transcription factors.

Result: Using scRNA-seq, we studied cells from patients with NB. NE cells exhibited superior specificity in contrast to other cell types. Among NE cells, C1 PCLAF + NE cells showed a close correlation with the genesis and advancement of NB. The key marker genes, cognate receptor pairing, developmental trajectories, metabolic pathways, transcription factors, and enrichment pathways in C1 PCLAF + NE cells, as well as the expression of cuproptosis in C1 PCLAF + NE cells, provided new ideas for exploring new therapeutic targets for NB.

Conclusion: The results revealed the specificity of malignant NE cells in NB, especially the key subset of C1 PCLAF + NE cells, which enhanced our understanding of the key role of the tumor microenvironment in the complexity of cancer progression. Of course, cell death played an important role in the progression of NB, which also promoted our research on new targets. The scrutiny of these findings proved advantageous in uncovering innovative therapeutic targets, thereby bolstering clinical interventions.