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

ABSTRACT: 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 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.

SUBMITTER: Liu Q

PROVIDER: S-EPMC9485279 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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

Liu Qingqing Q Wang Zhenni Z Jiang Yan Y Shao Fengling F Ma Yue Y Zhu Mingzhao M Luo Qing Q Bi Yang Y Cao Lijian L Peng Liang L Zhou Jianwu J Zhao Zhenzhen Z Deng Xiaobin X He Tong-Chuan TC Wang Shan S

Genes & diseases 20220204 6

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 peri ...[more]

PMID: 36157484

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Project description:BackgroundThe association between long noncoding RNAs (lncRNAs) and spontaneous regression of neuroblastoma (NB) has rarely been investigated and remains unknown.ObjectiveTo identify prognostic lncRNAs involved in the spontaneous regression of NB.MethodsDifferential expression analyses were performed between those samples with an outcome of death in stage 4 NB group and those samples with an outcome of survival in stage 4S NB group in two independent public datasets, respectively. Univariate Cox proportional hazard regression survival analysis was performed in each of the entire cohort to identify those lncRNAs significantly associated with overall survival (OS). Those lncRNAs independently associated with OS were then identified by multivariate Cox survival analysis and used to construct an lncRNA risk score.ResultsA total of 20 differentially expressed and survival-related lncRNAs were identified sharing between the two independent cohorts. The expression of each of these 20 lncRNAs was significantly correlated with the expression of NTRK1, which is a well-known factor involved in NB spontaneous regression. Four lncRNAs (LNC00839, FIRRE, LOC283177, and LOC101928100) were identified to be significantly associated with survival independent with each other and a four-lncRNA signature risk score was constructed. Patients with high lncRNA signature risk score had a significantly poorer OS and event-free survival than those with low lncRNA signature risk score. The four-lncRNA signature has a good performance in predicting survival independent with MYCN amplification (nonamplified vs amplified), age status (<18 months vs ≥18 months), risk status (low risk vs high risk), and International Neuroblastoma Staging System (INSS) stage (INSS 1/2/3/4S vs INSS 4).ConclusionsWe identified 20 survival-related lncRNAs that might be associated with the spontaneous regression of NB and developed a four-lncRNA signature risk score. The four-lncRNA signature is an independent prognostic factor for survival of NB patients.

Dataset Information

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

Publications

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

Similar Datasets

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