Single-cell landscape analysis reveals distinct regression trajectories and novel prognostic biomarkers in primary neuroblastoma

作者全名："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"

作者地址："[Liu, Qingqing; Wang, Zhenni; Shao, Fengling; Ma, Yue; Luo, Qing; Bi, Yang; Cao, Lijian; Peng, Liang; Zhou, Jianwu; Zhao, Zhenzhen; Deng, Xiaobin; Wang, Shan] Chongqing Med Univ, Childrens Hosp, Dept Pediat Surg Oncol, Chongqing 400014, Peoples R China; [Liu, Qingqing; Wang, Zhenni; Shao, Fengling; Ma, Yue; Luo, Qing; Bi, Yang; Cao, Lijian; Peng, Liang; Zhou, Jianwu; Zhao, Zhenzhen; Deng, Xiaobin; Wang, Shan] Minist Educ, Natl Clin Res Ctr Child Hlth & Disorders, Key Lab Child Dev & Disorders, Chongqing Key Lab Pediat, Chongqing 400014, Peoples R China; [Jiang, Yan] Singleron Biotechnol Co Ltd, Nanjing 211800, Jiangsu, Peoples R China; [Zhu, Mingzhao] Chinese Acad Sci, Inst Biophys, Key Lab Infect & Immun, Beijing 100101, Peoples R China; [He, Tong-Chuan] Univ Chicago, Med Ctr, Dept Orthopaed Surg & Rehabil Med, Mol & Oncol Lab, Chicago, IL 60637 USA"

通信作者："Wang, S (通讯作者)，Chongqing Med Univ, Childrens Hosp, Dept Pediat Surg Oncol, Chongqing 400014, Peoples R China."

来源：GENES & DISEASES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000870272900025

JCR分区：Q1

影响因子：6.8

年份：2022

卷号：9

期号：6

开始页：1624

结束页：1638

文献类型：Article

关键词：Neuroblastoma (NB); Prognostic biomarkers; Regression trajectory; Single-cell RNA sequencing (scRNA-seq)

摘要："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. How-ever, 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 dis-played 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 CCL2 and ZFP36, supporting a progressive pathway of spontaneous NB regression. We also identified prognostic markers (STMN2, TUBA1A, PAGE5, and ETV1) by evaluating intratumoral heterogeneity. Lastly, we determined that ITGB1 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. Copyright 2022, Chongqing Medical University. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/ by-nc-nd/4.0/)."

基金机构："Key Project of ""Research on Prevention and Control of Major Chronic Non-Communicable Diseases""; Ministry of Science and Technology of the People's Republic of China; National Key R&D Program of China [2018YFC1313000, 2018YFC1313004]; General Clinical Medical Research Program of Children's Hospital of Chongqing Medical University [YBXM-2019-003]; Chongqing Science and Technology Commission [cstc2019jscxmsxmX0220]"

基金资助正文："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), and the Chongqing Science and Technology Commission (No. cstc2019jscxmsxmX0220)."