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Construction and characterization of a cuproptosis- and immune checkpoint-based LncRNAs signature for breast cancer risk stratification

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Abstract

Background

Cuproptosis is the most recently identified form of cell death, and copper homeostasis is an important cancer therapeutic target. However, the therapeutic benefits of cuproptosis-targeted treatment in BRCA remain undetermined. This study utilized LncRNAs linked to cuproptosis genes and immune checkpoint genes to generate a BRCA predictive signature.

Methods

We screened a population of LncRNAs that correlated with both cuproptosis genes and immune checkpoint genes and used ten of these LncRNAs to construct a prognosis-predictive signature. We then validated and proved the efficacy of the signature in predicting the prognosis of BRCA patients. We also unraveled the relationship between the signature and the immunological milieu, immune function, and susceptibility to chemotherapy.

Results

The signature derived from the ten cuproptosis- and immune-related prognostic LncRNAs (CuImP-LncRNAs) can be implied to categorize patients into two groups, including the high- and low-risk groups. The value of the signature was validated, and the risk score was verified as an independent prognostic indicator. The TIME and TMB distribution patterns and chemosensitivity were depicted in the high- and low-risk groups, respectively. Patients of the high-risk group with a suppressive immunological intratumor context were more sensitive to a broad range of antitumor agents. In contrast, low-risk individuals with active immune function responded more favorably to immunotherapy.

Conclusion

Our findings provided a novel and effective model for predicting BRCA prognosis and the propensity to different treatment modalities, thus contributing to the optimization of personalized BRCA therapy in the future.

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Data availability

The datasets used in this study can be found in the TCGA database (https://portal.gdc.cancer.gov), GSEA (http://www.gsea-msigdb.org/gsea/index.jsp), TIMER database (http://cistrome.dfci.harvard.edu/TIMER/), and GDSC (https://www.cancerrxgene.org/).

Abbreviations

CuImP-LncRNAs:

Cuproptosis- and immune-related prognostic LncRNAs

TCGA:

The Cancer Genome Atlas

TIME:

Tumor immune microenvironment

TMB:

Tumor mutation burden

LASSO:

Least absolute shrinkage and selection operator

GDSC:

Genomics of drug sensitivity in cancer

OS:

Overall survival

PFS:

Progression-free survival

IPS:

Immunophenoscore

ROC:

Receiver operator characteristic

AUC:

Area under the ROC curve

PCA:

Principal component analysis

IC50:

Half-maximal inhibitory concentration

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Acknowledgements

We thank all research groups who established and updated all open-access databases used in this study.

Funding

This study was supported by grants from the Lanzhou Science and Technology Bureau (2022-ZD-62) and the Natural Science Foundation of Gansu Province (21JR7RA662).

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Authors and Affiliations

  1. Department of Medicine, Northwest Minzu University, Lanzhou, 730030, China

    Yan Li

  2. Gansu Province Maternal and Child-Care Hospital, Lanzhou, 730050, China

    Feiyang Na & Jianying Pei

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  1. Yan Li
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Contributions

YL and JP conceived and designed this study, and JP conducted the data collection and analyses. YL reviewed the analysis results and wrote the manuscript. FN revised the manuscript. All authors agreed to the final manuscript.

Corresponding author

Correspondence to Jianying Pei.

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Li, Y., Na, F. & Pei, J. Construction and characterization of a cuproptosis- and immune checkpoint-based LncRNAs signature for breast cancer risk stratification. Breast Cancer 30, 393–411 (2023). https://doi.org/10.1007/s12282-023-01434-9

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