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 pote...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 scRNAseq 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 CCL2 and ZFP36,supporting a progressive pathway of spontaneous NB regression.We also identified prognostic markers(STMN2,TUBA1A,PAGE5,and ETV1)by evaluating intra-tumoral 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.展开更多
基金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)the Chongqing Science and Technology Commission(No.cstc2019jscxmsxmX0220).
文摘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 scRNAseq 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 CCL2 and ZFP36,supporting a progressive pathway of spontaneous NB regression.We also identified prognostic markers(STMN2,TUBA1A,PAGE5,and ETV1)by evaluating intra-tumoral 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.
