Liu Qingqing, Wang Zhenni, Jiang Yan, Shao Fengling, Ma Yue, Zhu Mingzhao, Luo Qing, Bi Yang, Cao Lijian, Peng Liang, Zhou Jianwu, Zhao Zhenzhen, Deng Xiaobin, He Tong-Chuan, Wang Shan
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 400014, PR China.
Singleron Biotechnologies Co., Ltd, Nanjing, Jiangsu 211800, PR China.
Genes Dis. 2022 Feb 4;9(6):1624-1638. doi: 10.1016/j.gendis.2021.12.020. eCollection 2022 Nov.
Neuroblastoma (NB), which is the most common pediatric extracranial solid tumor, varies widely in its clinical presentation and outcome. NB has a unique ability to spontaneously differentiate and regress, suggesting a potential direction for therapeutic intervention. However, the underlying mechanisms of regression remain largely unknown, and more reliable prognostic biomarkers are needed for predicting trajectories for NB. We performed scRNA-seq analysis on 17 NB clinical samples and three peritumoral adrenal tissues. Primary NB displayed varied cell constitution, even among tumors of the same pathological subtype. Copy number variation patterns suggested that neuroendocrine cells represent the malignant cell type. Based on the differential expression of sets of related marker genes, a subgroup of neuroendocrine cells was identified and projected to differentiate into a subcluster of benign fibroblasts with highly expressed and , supporting a progressive pathway of spontaneous NB regression. We also identified prognostic markers ( and ) by evaluating intra-tumoral heterogeneity. Lastly, we determined that in M2-like macrophages was associated with favorable prognosis and may serve as a potential diagnostic marker and therapeutic target. In conclusion, our findings reveal novel mechanisms underlying regression and potential prognostic markers and therapeutic targets of NB.
神经母细胞瘤（NB）是最常见的小儿颅外实体瘤，其临床表现和预后差异很大。NB具有自发分化和消退的独特能力，这为治疗干预提供了一个潜在方向。然而，消退的潜在机制在很大程度上仍然未知，并且需要更可靠的预后生物标志物来预测NB的发展轨迹。我们对17个NB临床样本和三个瘤旁肾上腺组织进行了单细胞RNA测序（scRNA-seq）分析。原发性NB显示出不同的细胞组成，即使在相同病理亚型的肿瘤中也是如此。拷贝数变异模式表明神经内分泌细胞代表恶性细胞类型。基于相关标记基因集的差异表达，鉴定出神经内分泌细胞亚群，并预测其可分化为高表达 和 的良性成纤维细胞亚簇，支持NB自发消退的渐进途径。我们还通过评估肿瘤内异质性鉴定了预后标志物（ 和 ）。最后，我们确定M2样巨噬细胞中的 与良好预后相关，可能作为潜在的诊断标志物和治疗靶点。总之，我们的研究结果揭示了NB消退的新机制以及潜在的预后标志物和治疗靶点。
