Multi-omics analysis identifies stemness-driven molecular subtypes, prognostic signature, epigenetic target APCDD1, and drug candidate Leflunomide in Wilms tumor
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By
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Huifang Du
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Yifeng Zheng
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Chentao Zhu
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Yang Guo
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Pengfei Li
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Peng Hong
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May 25, 2026
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Objective:
To investigate the molecular basis of stemness features in Wilms tumor (WT) and identify prognostic indicators and potential therapeutic agents.
Key Findings:
- Blastemal cells exhibited the highest stemness score, correlating with worse prognosis.
- C1 subtype showed higher stemness and an immunosuppressive tumor microenvironment with dysfunctional NK cells.
- APCDD1 expression can be restored by the demethylating agent Decitabine.
- Elevated APCDD1 expression has a protective causal effect on WT susceptibility.
- Leflunomide inhibited WT cell proliferation, migration, invasion, and induced apoptosis in a dose-dependent manner.
Interpretation:
Limitations:
- The study primarily focuses on molecular and cellular mechanisms without extensive clinical validation.
- Further research is needed to fully understand the translational implications of findings.
Conclusion: