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基于CD8+T细胞单细胞测序的三阴性乳腺癌预后及免疫治疗疗效预测模型

The Prediction Model for Triple-Negative Breast Cancer Prognosis and Immunotherapy Efficacy Based on Single-Cell Sequencing of CD8+ T cells.

作者信息

Yi Jiarong, Qiao Yejun, Xiong Zhengchong, Feng Jikun, Zouxu Xiazi, Zeyu Shuang, Wang Xi

机构信息

Department of Breast Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.

Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.

出版信息

J Cancer. 2025 Jul 24;16(11):3343-3354. doi: 10.7150/jca.115507. eCollection 2025.

Abstract

Triple-negative breast cancer (TNBC) exhibits a higher propensity for recurrence, distant metastasis, and mortality than the other subtypes of breast cancer. TNBC is primarily attributed to the lack of expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Single-cell sequencing results of CD8 T cells in TNBC patients were screened for differentially expressed and immune-related genes. The selected genes were then analyzed with immunohistochemistry for their prognostic effects. Additionally, a regression model was constructed to ascertain the gene expression score and classify patients into high- and low-risk groups. We further analyzed the impact of gene expression on prognosis based on risk grouping and evaluated its potential as a prognostic predictor for TNBC patients. This analysis was validated using PCR and the prognostic data from patient samples. We also investigated the effect of risk grouping on immunotherapy in TNBC patients and evaluated its potential to predict the efficacy of immunotherapy in TNBC patients. Single-cell sequencing of CD8 T cells from TNBC patients identified 191 differentially expressed genes. Among them, XCL1, RASGRP1, CTSD, and AIP were reported to be independent prognostic factors for TNBC. The results were verified through immunohistochemistry. Additionally, a regression analysis model was constructed using these four genes to classify patients into risk groups. The high-risk group correlated with a poor prognosis in patients and could serve as an independent prognostic factor for TNBC. The results were further validated through PCR. Notably, patients in the low-risk group displayed a better response to immunotherapy. Based on the single-cell sequencing results of CD8 T cells from TNBC patients, a prediction model was established, which facilitated prognosis prediction in TNBC patients and evaluated the patients' response to immunotherapy. In summation, this model could potentially assist in improving the efficacy of TNBC immunotherapy.

摘要

三阴性乳腺癌(TNBC)比其他亚型的乳腺癌具有更高的复发、远处转移和死亡倾向。TNBC主要归因于雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体2(HER2)的表达缺失。对TNBC患者CD8 T细胞的单细胞测序结果进行筛选,以找出差异表达基因和免疫相关基因。然后通过免疫组织化学分析所选基因的预后作用。此外,构建了一个回归模型来确定基因表达评分,并将患者分为高风险组和低风险组。我们根据风险分组进一步分析了基因表达对预后的影响,并评估了其作为TNBC患者预后预测指标的潜力。该分析通过聚合酶链反应(PCR)和患者样本的预后数据进行了验证。我们还研究了风险分组对TNBC患者免疫治疗的影响,并评估了其预测TNBC患者免疫治疗疗效的潜力。对TNBC患者的CD8 T细胞进行单细胞测序,鉴定出191个差异表达基因。其中,XCL1、RASGRP1、CTSD和AIP被报道为TNBC的独立预后因素。结果通过免疫组织化学得到验证。此外,利用这四个基因构建了回归分析模型,将患者分为风险组。高风险组患者的预后较差,可作为TNBC的独立预后因素。结果通过PCR进一步验证。值得注意的是,低风险组患者对免疫治疗的反应更好。基于TNBC患者CD8 T细胞的单细胞测序结果,建立了一个预测模型,该模型有助于TNBC患者的预后预测,并评估患者对免疫治疗的反应。总之,该模型可能有助于提高TNBC免疫治疗的疗效。

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