Single-cell transcriptome sequencing reveals tumor heterogeneity in family neuroblastoma

Yunlong Zhang; Yue Ma; Qingqing Liu; Yifei Du; Liang Peng; Jianwu Zhou; Zhenzhen Zhao; Changchun Li; Shan Wang

doi:10.3389/fimmu.2023.1197773

Single-cell transcriptome sequencing reveals tumor heterogeneity in family neuroblastoma

Front Immunol. 2023 Sep 18:14:1197773. doi: 10.3389/fimmu.2023.1197773. eCollection 2023.

Authors

Yunlong Zhang¹, Yue Ma¹, Qingqing Liu¹, Yifei Du¹, Liang Peng¹, Jianwu Zhou¹, Zhenzhen Zhao¹, Changchun Li¹, Shan Wang¹

Affiliation

¹ 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.

Abstract

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 SDHD 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.

Keywords: SDHD; cancer-associated fibroblasts (CAF); family neuroblastoma (FNB); single-cell RNA sequencing (scRNA-seq); single-cell flux estimation analysis (scFEA); tumor microenvironment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Ganglioneuroblastoma* / metabolism
Genetic Predisposition to Disease
Humans
Neuroblastoma* / pathology
Prognosis
Transcriptome

Grants and funding

This work was supported in part by research grants from the Key Project of “Research on Prevention and Control of Major Chronic Non-Communicable Diseases”, the Ministry of Science and Technology of the People’s Republic of China, National Key R&D Program of China (No. 2018YFC1313000, 2018YFC1313004), the General Clinical Medical Research Program of Children’s Hospital of Chongqing Medical University (No. YBXM-2019-003).