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CXCL9+巨噬细胞浸润赋予乳腺癌良好预后:来自整合单细胞 RNA 和 bulk RNA 测序研究的见解

英文原题:Infiltration of CXCL9+ macrophages confers a favorable prognosis in breast cancer: Insights from an integrated single-cell RNA and bulk RNA sequencing study.

查看英文原题

Infiltration of CXCL9+ macrophages confers a favorable prognosis in breast cancer: Insights from an integrated single-cell RNA and bulk RNA sequencing study.

PubMed 2025/12/01(内容时间) PLoS One Q2 · IF 2.8(JCR 2025)

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研究概要

CXCL9+巨噬细胞可能在抑制乳腺癌中发挥重要作用,其浸润至肿瘤组织与乳腺癌患者生存改善相关。靶向 CXCL9+巨噬细胞的免疫治疗作为一种治疗策略具有巨大潜力。

研究思路结论见上方概要

乳腺癌是女性中最常见的癌症,也是导致疾病相关死亡率的主要原因之一。尽管诊断技术的进步和医学知识的广泛传播改善了治疗效果,但针对肿瘤微环境的免疫疗法为进一步减轻疾病负担提供了一种有前景的方法。

我们首先利用单细胞RNA测序探索了乳腺癌肿瘤内的细胞异质性,随后结合批量RNA测序使用去卷积算法分析了各种细胞类型的浸润水平与生存预后之间的关联。我们的分析发现CXCL9+巨噬细胞与改善的生存结局相关。接下来,使用WGCNA识别与CXCL9+巨噬细胞浸润相关的基因,并基于这些基因构建了生存风险模型。最后,通过实验验证了CXCL9+巨噬细胞对乳腺癌细胞的影响。

我们发现CXCL9+巨噬细胞主要通过CXCL9/10/11-CXCR3轴与细胞因子相互作用并激活T细胞和NK细胞。在bulk RNA测序中观察到的浸润增加与患者生存改善相关。基于CXCL9+巨噬细胞浸润相关基因构建的风险模型在预测患者生存结局方面表现出较强效力。最后,体外实验证实CXCL9+巨噬细胞抑制了乳腺癌细胞的活力。

展开英文摘要原文

Breast cancer is the most common cancer among women and a leading contributor to disease-related mortality. While advancements in diagnostic techniques and the widespread dissemination of medical knowledge have improved outcomes, immunotherapy targeting the tumor microenvironment offers a promising approach to further reducing the disease burden.

We first explored cellular heterogeneity within breast cancer tumors using single-cell RNA sequencing and subsequently analyzed the association between the infiltration levels of various cell types and survival prognosis using a deconvolution algorithm combined with bulk RNA sequencing. Our analysis identified CXCL9 + macrophages as being associated with improved survival outcomes. Next, WGCNA was used to identify genes related to CXCL9 + macrophage infiltration, and a survival risk model was constructed based on these genes. Finally, experiments were conducted to validate the effects of CXCL9 + macrophages on breast cancer cells.

We found that CXCL9 + macrophage primarily interacted with cytokines and activated T and NK cells through the CXCL9/10/11-CXCR3 axis. Increased infiltration, as observed in bulk RNA sequencing, was associated with improved patient survival. The risk model constructed based on CXCL9 + macrophage infiltration-related genes demonstrated strong efficacy in predicting patient survival outcomes. Finally, in vitro experiments confirmed that CXCL9 + macrophages inhibited the viability of breast cancer cells.

CXCL9 + macrophages could play a significant role in inhibiting breast cancer, and their infiltration into tumor tissues is associated with improved survival in breast cancer patients. Immunotherapy targeting CXCL9 + macrophages hold great potential as a therapeutic strategy.

论文信息

作者
Liang B、Duan Z、Long S、Zhou P
单位
Department of General Surgery (Breast Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, People's Republic of China.China
期刊
PloS one2025
原文标识
PubMed 41325308 · DOI 10.1371/journal.pone.0337175