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A CD8+ T Cell-Related Genes Expression Signature Predicts Prognosis and the Efficacy of Immunotherapy in Breast Cancer

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Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

Immunotherapy has been applied to patients with breast cancer. However, only part of patients benefits from the current immunotherapy. Accurate prediction of individual response to immunotherapy can be beneficial for breast cancer management. CD8+ T cells are the main force of anti-tumor immunity. This study aimed to establish a CD8+ T cell-related gene expression signature for prediction of breast cancer prognostic and immunotherapy efficacy. RNA-seq transcriptomic data was the basics of this research. Weighted gene co-expression network analysis (WGCNA) and the least absolute shrinkage and selection operator (LASSO) Cox regression analysis established the prognostic signature. We identified 290 CD8+ T cell-related genes in the training set and established a risk-score model based on 8-genes panel (SOCS1, IL10, CAMK4, CXCL13, KIR2DS4, TESPA1, CD70 and ICAM4). Subsequently, univariate Cox regression analysis suggested that high risk-score was a risk factor for breast cancer (HR = 3.1, 95%CI 2.0–4.8, P < 0.001). In tumor microenvironment, high-risk tumors present decreased tumor infiltrating CD8+ T cells and increased M2 macrophages. The low-risk patients may benefit more from immune checkpoint blockade immunotherapy than the high-risk patients. Moreover, breast tumors which sensitive to immune checkpoint inhibitor (ICI) showed higher IL10 expression.

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Data Availability

The publicly available gene expression data used in the present study can be accessed from the UCSC Xena website (https://xenabrowser.net) and GEO database website (https://www.ncbi.nlm.nih.gov/gds).

Abbreviations

TCGA-BRCA:

The Cancer Genome Atlas- breast cancer

ssGSEA:

Single-sample gene set enrichment analysis

WGCNA:

Weighted gene co-expression network analysis

OS:

Overall survival

LASSO:

Least absolute shrinkage and selection operator

KEGG:

Kyoto Encyclopedia of Genes and Genomes

ROC:

Receiver operating characteristic

AUC:

Area under the ROC curve

ICI:

Immune checkpoints inhibitors

IPS:

Immunophenoscore

CR:

Complete response

PR:

Partial response

SD:

Stable disease

PD:

Progressive disease

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Acknowledgements

We thank all the contributors of data involved in this study.

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Author notes

  1. Lian-hua Lv and Jia-rong Lu contributed equally to this work.

Authors and Affiliations

  1. The Second Clinical Medical College, Guangxi Medical University, Nanning, 530021, Guangxi, China

    Lian-hua Lv

  2. The First Clinical Medical College, Guangxi Medical University, Nanning, 530021, Guangxi, China

    Jia-rong Lu, Tao Zhao & Hai-qi Liang

  3. Nursing College, Guangxi Medical University, Nanning, 530021, Guangxi, China

    Jing-li Liu

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  1. Lian-hua Lv
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Contributions

HL and LL designed and conceived the study. TZ downloaded the data from online databases. HL and JL analyzed the data. LL, TZ and JL wrote the manuscript.

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Correspondence to Hai-qi Liang.

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Lv, Lh., Lu, Jr., Zhao, T. et al. A CD8+ T Cell-Related Genes Expression Signature Predicts Prognosis and the Efficacy of Immunotherapy in Breast Cancer. J Mammary Gland Biol Neoplasia 27, 53–65 (2022). https://doi.org/10.1007/s10911-022-09510-0

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