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Integrating bulk-seq and single-cell-seq reveals disulfidptosis potential index associating with neuroblastoma prognosis and immune infiltration

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Abstract

Purpose

Neuroblastoma is a challenging pediatric tumor with a need for improved treatment strategies. This study explores the role of disulfidptosis, a form of cell death induced by intracellular disulfide accumulation, in neuroblastoma and its implications for prognosis and immune infiltration.

Methods

We subgrouped neuroblastoma samples based on disulfidptosis-related gene expression and constructed a disulfidptosis potential index (DPI) to quantify disulfidptosis levels in neurobalstoma. The correlation between DPI, outcome, immune infiltration, and drug sensitivity were explored.

Results

Combing RNA-seq and single-cell dataset, we found that higher disulfidptosis potential index (DPI) is associated with poorer outcomes in neuroblastoma patients, indicating the detrimental impact of enhanced disulfide stress and cellular dysfunction. Furthermore, we found that higher DPI is correlated with reduced immune infiltration within the tumor microenvironment, highlighting an immunosuppressive milieu in high DPI neuroblastomas. The DPI-high neuroblastoma may benefit from the estrogen pathway related drug fulvestrant.

Conclusion

Overall, this study highlights the significance of disulfidptosis as a potential therapeutic target and underscores the importance of integrating immune modulation strategies, offering new avenues for improved management of neuroblastoma.

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Data availability

The data analyzed in this study were obtained from Gene Expression Omnibus (GEO) at GSE49710, ArrayExpress at E-MTAB-8248. The codes used during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

We would like to acknowledge Selina Jansky and Frank Westermann from the German Cancer Research Center for kindly providing single-cell neuroblastoma datasets.

Funding

This work was supported by grants from the Tianjin Health Technology Project (Grant no. 2022QN106).

Author information

Authors and Affiliations

  1. Tianjin Cancer Hospital Airport Hospital, National Clinical Research Center for Cancer, Tianjin, China

    Aiguo Zhu, Xin Li & Jian Wang

  2. Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060, China

    Aiguo Zhu, Xin Li & Jian Wang

Authors
  1. Aiguo Zhu
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  2. Xin Li
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  3. Jian Wang
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Contributions

A.Z. performed data analysis and original draft writing; X.L. and J.W. reviewed and edited the manuscript; J.W. performed the study concept and design; J.W. is the guarantor of this work and takes responsibility for the integrity of the data and accuracy of the data analysis. All the authors have read and approved the final manuscript.

Corresponding authors

Correspondence to Xin Li or Jian Wang.

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Conflict of interest

The authors declare that they have no competing interests.

Ethics approval

As all data analyzed in this study were obtained from publicly available datasets, no ethics approval form was required for this manuscript.

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Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (EPS 140 KB) Supplementary Figure 1 | Flowchart of the Study

432_2023_5392_MOESM2_ESM.tif

Supplementary file2 (TIF 8716 KB) Supplementary Figure 2 | Expression Distribution of Disulfidptosis-Related Gene Set across Clusters

Supplementary file3 (TIF 1102 KB) Supplementary Figure 3 | Validation of DPI Feasibility Using an External Dataset

432_2023_5392_MOESM4_ESM.tif

Supplementary file4 (TIF 3635 KB) Supplementary Figure 4 | Enrichment Analysis Results of GSEA in DPI-High and DPI-Low Groups

432_2023_5392_MOESM5_ESM.tif

Supplementary file5 (TIF 933 KB) Supplementary Figure 5 | Enhanced Estrogen Signaling Pathway Activity and Drug Sensitivity in High-DPI Neuroblastomas in Validation Cohort

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Zhu, A., Li, X. & Wang, J. Integrating bulk-seq and single-cell-seq reveals disulfidptosis potential index associating with neuroblastoma prognosis and immune infiltration. J Cancer Res Clin Oncol 149, 16647–16658 (2023). https://doi.org/10.1007/s00432-023-05392-9

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  • DOI: https://doi.org/10.1007/s00432-023-05392-9

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