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Research Article

Differentiation Potential of Hypodifferentiated Subsets of Nephrogenic Rests and Its Relationship to Prognosis in Wilms Tumor

, , , , , , , , , , & ORCID Icon show all
Pages 123-139 | Received 09 Oct 2023, Accepted 02 Jan 2024, Published online: 12 Jan 2024
 

Abstract

Background Wilms tumor (WT) is highly curable, although anaplastic histology or relapse imparts a worse prognosis. Nephrogenic rests (NR) associated with a high risk of developing WT are abnormally retained embryonic kidney precursor cells. Methods After pseudo-time analysis using single-cell RNA sequencing (scRNA-seq) data, we generated and validated a WT differentiation-related gene (WTDRG) signature to predict overall survival (OS) in children with a poor OS. Results A differentiation trajectory from NR to WT was identified and showed that hypodifferentiated subsets of NR could differentiate into WT. Classification of WT children with anaplastic histology or relapse based on the expression patterns of WTDRGs suggested that patients with relatively high levels of hypodifferentiated NR presented a poorer prognosis. A WTDRG-based risk model and a clinically applicable nomogram was developed. Conclusions These findings may inform oncogenesis of WT and interventions directed toward poor prognosis in WT children of anaplastic histology or relapse.

Author contributions

SW designed and guided the study. ML, JL, CY and JZ performed the analysis of the data. LW, YH and LC helped with data and reference collection. RH, YL and MS generated the figures and tables. All authors contributed to manuscript writing and revision, and approved the submitted version.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [No. 82071632], the Innovation Program for Chongqing’s Overseas Returnees [cx2019030], the Senior Medical Talents Program of Chongqing for Young and Middle-Aged and the Program for Youth Innovation in Future Medicine, Chongqing Medical University [W0069].

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