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Open Access 01-12-2023 | Breast Cancer | Research article

The expression profiles of signature genes from CD103⁺LAG3⁺ tumour-infiltrating lymphocyte subsets predict breast cancer survival

Authors: Zi-An Xia, Can Lu, Can Pan, Jia Li, Jun Li, Yitao Mao, Lunquan Sun, Jiang He

Published in: BMC Medicine | Issue 1/2023

Abstract

Background

Tumour-infiltrating lymphocytes (TILs), including T and B cells, have been demonstrated to be associated with tumour progression. However, the different subpopulations of TILs and their roles in breast cancer remain poorly understood. Large-scale analysis using multiomics data could uncover potential mechanisms and provide promising biomarkers for predicting immunotherapy response.

Methods

Single-cell transcriptome data for breast cancer samples were analysed to identify unique TIL subsets. Based on the expression profiles of marker genes in these subsets, a TIL-related prognostic model was developed by univariate and multivariate Cox analyses and LASSO regression for the TCGA training cohort containing 1089 breast cancer patients. Multiplex immunohistochemistry was used to confirm the presence of TIL subsets in breast cancer samples. The model was validated with a large-scale transcriptomic dataset for 3619 breast cancer patients, including the METABRIC cohort, six chemotherapy transcriptomic cohorts, and two immunotherapy transcriptomic cohorts.

Results

We identified two TIL subsets with high expression of CD103 and LAG3 (CD103⁺LAG3⁺), including a CD8⁺ T-cell subset and a B-cell subset. Based on the expression profiles of marker genes in these two subpopulations, we further developed a CD103⁺LAG3⁺ TIL-related prognostic model (CLTRP) based on CXCL13 and BIRC3 genes for predicting the prognosis of breast cancer patients. CLTRP-low patients had a better prognosis than CLTRP-high patients. The comprehensive results showed that a low CLTRP score was associated with a high TP53 mutation rate, high infiltration of CD8 T cells, helper T cells, and CD4 T cells, high sensitivity to chemotherapeutic drugs, and a good response to immunotherapy. In contrast, a high CLTRP score was correlated with a low TP53 mutation rate, high infiltration of M0 and M2 macrophages, low sensitivity to chemotherapeutic drugs, and a poor response to immunotherapy.

Conclusions

Our present study showed that the CLTRP score is a promising biomarker for distinguishing prognosis, drug sensitivity, molecular and immune characteristics, and immunotherapy outcomes in breast cancer patients. The CLTRP could serve as a valuable tool for clinical decision making regarding immunotherapy.

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Title: The expression profiles of signature genes from CD103+LAG3+ tumour-infiltrating lymphocyte subsets predict breast cancer survival
Authors: Zi-An Xia
Can Lu
Can Pan
Jia Li
Jun Li
Yitao Mao
Lunquan Sun
Jiang He
Publication date: 01-12-2023
Publisher: BioMed Central
Keywords: Breast Cancer
Breast Cancer
Cytostatic Therapy
Published in: BMC Medicine / Issue 1/2023
Electronic ISSN: 1741-7015
DOI: https://doi.org/10.1186/s12916-023-02960-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The expression profiles of signature genes from CD103⁺LAG3⁺ tumour-infiltrating lymphocyte subsets predict breast cancer survival

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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