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05.09.2022 | Original Article

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

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

Erschienen in: Hepatology International | Ausgabe 6/2022

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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.

Graphical abstract

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Titel: Development and experimental verification of a prognosis model for cuproptosis-related subtypes in HCC
verfasst von: Yixiu Wang
Yongfa Zhang
Longrong Wang
Ning Zhang
Weiqi Xu
Jiamin Zhou
Yiming Zhao
Weiping Zhu
Ti Zhang
Lu Wang
Publikationsdatum: 05.09.2022
Verlag: Springer India
Erschienen in: Hepatology International / Ausgabe 6/2022
Print ISSN: 1936-0533
Elektronische ISSN: 1936-0541
DOI: https://doi.org/10.1007/s12072-022-10381-0

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