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Development and experimental verification of a prognosis model for cuproptosis-related subtypes in HCC

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Abstract

Background

Cuproptosis is a recently discovered mechanism of programmed cell death caused by intracellular aggregation of mitochondrial lipoylated proteins and destabilization of iron-sulfur proteins triggered by copper. Hepatocellular carcinoma (HCC) is a common malignant tumor with a poor prognosis. We aimed to predict the survival of patients with HCC using the cuproptosis-related gene (CRG) expression.

Methods

We analyzed the expression, methylation, and mutation status of CRGs in 538 HCC patients and correlated the date with clinical prognosis. HCC patients were divided into two clusters based on their CRG expression. The relationship between CRGs, risk genes, and the immune microenvironment was analyzed using the CIBERSORT algorithm and the single-cell data analysis method. A cuproptosis risk model was constructed according to the five risk genes using the LASSO COX method. To facilitate the clinical applicability of the proposed risk model, we constructed a nomogram and conducted an antineoplastic drug sensitivity analysis.

Results

Our results suggest that the expression levels of CRGs in HCC are regulated by methylation. The prognoses were significantly different between the patients of the two clusters. The prognostic risk score positively correlated with memory T cell activation and negatively correlated with natural killer (NK) and regulatory T cell activation.

Conclusion

Our findings indicate the involvement of CRG regulation in HCC and provide new insights into prognosis assessment. Drug sensitivity analysis predicted drug candidates for the treatment of patients with different HCC subtypes.

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Availability of data and material

The datasets analyzed for this study can be found in the TCGA (http://www.cancer.gov/tcga) and GEO (https://www.ncbi.nlm.nih.gov/geo).

Code availability

The code data are available from the corresponding author on request.

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Funding

This study was supported by grants from the Clinical Research Plan of SHDC (SHDC2020CR4018), the National Natural Science Foundation of China (81902907 and 81874182) and Shanghai Pujiang Program (2019PJD008).

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Author notes

  1. Wang Yixiu, Zhang Yongfa, and Wang Longrong have contributed equally to this work.

Authors and Affiliations

  1. Qingdao Institute，Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China

    Yixiu Wang

  2. Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China

    Yixiu Wang, Yongfa Zhang, Longrong Wang, Ning Zhang, Weiqi Xu, Jiamin Zhou, Yiming Zhao, Weiping Zhu, Ti Zhang & Lu Wang

Authors
  1. Yixiu Wang
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  2. Yongfa Zhang
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  3. Longrong Wang
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  4. Ning Zhang
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  5. Weiqi Xu
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  6. Jiamin Zhou
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  7. Yiming Zhao
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  8. Weiping Zhu
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  9. Ti Zhang
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  10. Lu Wang
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Contributions

WY, WL, ZT: contributed to the conception of the study; WY, ZY, WL: performed the experiment; XW, ZN, ZY: contributed significantly to analysis and manuscript preparation; WY, ZJ: performed the data analyses and wrote the manuscript; XW, ZW: helped perform the analysis with constructive discussions.

Corresponding authors

Correspondence to Weiping Zhu, Ti Zhang or Lu Wang.

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Wang, Y., Zhang, Y., Wang, L. et al. Development and experimental verification of a prognosis model for cuproptosis-related subtypes in HCC. Hepatol Int 16, 1435–1447 (2022). https://doi.org/10.1007/s12072-022-10381-0

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  • DOI: https://doi.org/10.1007/s12072-022-10381-0

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