Department of Pediatric Surgical Oncology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China.
Front Immunol. 2023 Sep 18;14:1197773. doi: 10.3389/fimmu.2023.1197773. eCollection 2023.
Neuroblastoma(NB) is the most common extracranial solid tumor in childhood, and it is now believed that some patients with NB have an underlying genetic susceptibility, which may be one of the reasons for the multiplicity of NB patients within a family line. Even within the same family, the samples show great variation and can present as ganglioneuroblastoma or even benign ganglioneuroma. The genomics of NB is still unclear and more in-depth studies are needed to reveal its key components. We first performed single-cell RNA sequencing(sc-RNAseq) analysis on clinical specimens of two family neuroblastoma(FNB) and four sporadic NB cases. A complete transcriptional profile of FNB was constructed from 18,394 cells from FNB, and we found that may be genetically associated with FNB and identified a prognostic related CAF subtype in FNB: Fib-4. Single-cell flux estimation analysis (scFEA) results showed that malignant cells were associated with arginine spermine, oxaloacetate and hypoxanthine, and that malignant cells metabolize lactate at lower levels than T cells. Our study provides new resources and ideas for the development of the genomics of family NB, and the mechanisms of cell-to-cell interactions and communication and the metabolic landscape will provide new therapeutic targets.
神经母细胞瘤（NB）是儿童期最常见的颅外实体瘤，现在认为一些 NB 患者存在潜在的遗传易感性，这可能是家族中出现多个 NB 患者的原因之一。即使在同一家庭中，样本也表现出很大的差异，可表现为神经节母细胞瘤，甚至良性神经节细胞瘤。NB 的基因组学仍不清楚，需要更深入的研究来揭示其关键成分。我们首先对两个家族性神经母细胞瘤（FNB）和四个散发性神经母细胞瘤病例的临床标本进行了单细胞 RNA 测序（sc-RNAseq）分析。从 FNB 的 18394 个细胞中构建了 FNB 的完整转录谱，我们发现可能与 FNB 具有遗传相关性，并在 FNB 中鉴定出与预后相关的 CAF 亚型：Fib-4。单细胞通量估计分析（scFEA）结果表明，恶性细胞与精氨酸亚精胺、草酰乙酸和次黄嘌呤有关，恶性细胞的乳酸代谢水平低于 T 细胞。我们的研究为家族性 NB 的基因组学发展提供了新的资源和思路，细胞间相互作用和通讯的机制以及代谢景观将为新的治疗靶点提供依据。
