Chen Yi, Anwar Munawar, Wang Xiaoli, Zhang Boxiang, Ma Binlin
Department of Breast and Thyroid Surgery, Xinjiang Key Laboratory of Oncology, The Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi, 830011, Xinjiang Uygur, China.
The Clinical Medical Research Center of Breast and Thyroid Tumor in Xinjiang, Urumqi, 830011, Xinjiang Uygur, China.
Discov Oncol. 2025 Jun 1;16(1):977. doi: 10.1007/s12672-025-02811-w.
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.
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.
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.
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.
白细胞介素-27受体α（IL27RA）是白细胞介素-27受体的关键亚基，在T细胞介导的免疫中起重要作用。然而，其在乳腺癌中的相关性以及对免疫治疗的反应仍未得到探索。
我们整合了来自TCGA、GEO和scRNA-seq数据集的批量和单细胞RNA测序数据，以分析IL27RA的表达、预后、免疫浸润和治疗反应。使用TIDE和免疫检查点治疗的临床队列来评估免疫治疗反应性。使用GDSC数据预测化疗敏感性，并通过蛋白质印迹法验证IL27RA蛋白表达。
IL27RA在乳腺癌中表达下调，但高表达与良好的生存率相关。它主要在T细胞中表达，特别是CD8⁺亚群，并与丰富的免疫浸润和升高的检查点基因表达相关。IL27RA高表达患者的TIDE评分较低，在ICI治疗的队列中预后较好，对多种化疗药物的敏感性较高。
IL27RA是一种潜在的免疫生物标志物，可反映炎症性肿瘤微环境，并预测乳腺癌免疫治疗和化疗的获益。这些发现为使用单细胞转录组数据进行基于免疫的分层提供了新的见解。
