Integrative transcriptomic and single-cell analysis reveals IL27RA as a key immune regulator and therapeutic indicator in breast cancer

Integrative transcriptomic and single-cell analysis reveals IL27RA as a key immune regulator and therapeutic indicator in breast cancer

Abstract Background Interleukin-27 receptor alpha (IL27RA), a key subunit of the interleukin-27 receptor, plays an essential role in T cell–mediated immunity. However, its relevance in breast cancer and response to immunotherapy remains unexplored. Methods We integrated bulk and single-cell RNA sequ...

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Bibliographic Details
Main Authors: Yi Chen, Munawar Anwar, Xiaoli Wang, Boxiang Zhang, Binlin Ma
Format: Article
Language:English
Published: Springer 2025-06-01
Series:Discover Oncology
Subjects:
Breast cancer
IL27RA,
Tumor immune microenvironment
Single-cell RNA sequencing,
Immunotherapy response
Online Access:https://doi.org/10.1007/s12672-025-02811-w
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Summary:Abstract Background Interleukin-27 receptor alpha (IL27RA), a key subunit of the interleukin-27 receptor, plays an essential role in T cell–mediated immunity. However, its relevance in breast cancer and response to immunotherapy remains unexplored. Methods We integrated bulk and single-cell RNA sequencing data from TCGA, GEO, and scRNA-seq datasets to analyze IL27RA expression, prognosis, immune infiltration, and treatment response. TIDE and immune checkpoint–treated clinical cohorts were used to assess immunotherapy responsiveness. Chemotherapy sensitivity was predicted using GDSC data, and IL27RA protein expression was validated by Western blot. Results IL27RA was downregulated in breast cancer but high expression correlated with favorable survival. It was primarily expressed in T cells, particularly CD8⁺ subsets, and associated with enriched immune infiltration and elevated checkpoint gene expression. IL27RA high-expression patients showed lower TIDE scores, better outcomes in ICI-treated cohorts, and higher sensitivity to multiple chemotherapeutic agents. Conclusion IL27RA is a potential immune biomarker that reflects an inflamed tumor microenvironment and predicts benefit from immunotherapy and chemotherapy in breast cancer. These findings provide novel insights into immune-based stratification using single-cell transcriptomic data.
ISSN:2730-6011

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