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空间转录组学解码乳腺癌微环境异质性:从多维动态分析到精准治疗蓝图构建

Spatial Transcriptomics Decodes Breast Cancer Microenvironment Heterogeneity: From Multidimensional Dynamic Profiling to Precision Therapy Blueprint Construction.

作者信息

Ma Aolong, Xiang Lingyan, Yuan Jingping, Wang Qianwen, Zhao Lina, Yan Honglin

机构信息

Department of Pathology, Renmin Hospital of Wuhan University, Wuhan 430060, China.

出版信息

Biomolecules. 2025 Jul 24;15(8):1067. doi: 10.3390/biom15081067.

DOI:10.3390/biom15081067
PMID:40867511
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12383931/
Abstract

Breast cancer, the most prevalent malignancy among women worldwide, exhibits significant heterogeneity, particularly in the tumor microenvironment (TME), which poses challenges for treatment. Spatial transcriptomics (ST) has emerged as a transformative technology, enabling gene expression analysis while preserving tissue spatial architecture. This provides unprecedented insights into tumor heterogeneity, cellular interactions, and disease mechanisms, offering a powerful tool for advancing breast cancer research and therapy. This review aims to synthesize the applications of ST in breast cancer research, focusing on its role in decoding tumor heterogeneity, characterizing the TME, elucidating progression and metastasis dynamics, and predicting therapeutic responses. We also explore how ST can bridge molecular profiling with clinical translation to enhance precision therapy. The key scientific concepts of review included the following: We summarize the technological advancements in ST, including imaging-based and sequencing-based methods, and their applications in breast cancer. Key findings highlight how ST resolves spatial heterogeneity across molecular subtypes and histological variants. ST reveals the dynamic interplay between tumor cells, immune cells, and stromal components, uncovering mechanisms of immune evasion, metabolic reprogramming, and therapeutic resistance. Additionally, ST identifies spatial prognostic markers and predicts responses to chemotherapy, targeted therapy, and immunotherapy. We propose that ST serves as a hub for integrating multi-omics data, offering a roadmap for precision oncology and personalized treatment strategies in breast cancer.

摘要

乳腺癌是全球女性中最常见的恶性肿瘤,具有显著的异质性,尤其是在肿瘤微环境(TME)中,这给治疗带来了挑战。空间转录组学(ST)已成为一项变革性技术,能够在保留组织空间结构的同时进行基因表达分析。这为肿瘤异质性、细胞间相互作用和疾病机制提供了前所未有的见解,为推进乳腺癌研究和治疗提供了强大工具。本综述旨在综合ST在乳腺癌研究中的应用,重点关注其在解码肿瘤异质性、表征TME、阐明进展和转移动态以及预测治疗反应方面的作用。我们还探讨了ST如何将分子谱分析与临床转化联系起来,以增强精准治疗。综述的关键科学概念包括以下内容:我们总结了ST的技术进展,包括基于成像和基于测序的方法,以及它们在乳腺癌中的应用。主要发现突出了ST如何解决不同分子亚型和组织学变体之间的空间异质性。ST揭示了肿瘤细胞、免疫细胞和基质成分之间的动态相互作用,揭示了免疫逃逸、代谢重编程和治疗耐药的机制。此外,ST还能识别空间预后标志物,并预测对化疗、靶向治疗和免疫治疗的反应。我们认为,ST作为整合多组学数据的枢纽,为乳腺癌的精准肿瘤学和个性化治疗策略提供了路线图。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff22/12383931/b5eae7dc77f1/biomolecules-15-01067-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff22/12383931/218baa164769/biomolecules-15-01067-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff22/12383931/b5eae7dc77f1/biomolecules-15-01067-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff22/12383931/218baa164769/biomolecules-15-01067-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff22/12383931/b5eae7dc77f1/biomolecules-15-01067-g002.jpg

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本文引用的文献

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Spatial transcriptomics in breast cancer: providing insight into tumor heterogeneity and promoting individualized therapy.乳腺癌中的空间转录组学:洞察肿瘤异质性并推动个体化治疗。
Front Immunol. 2024 Dec 19;15:1499301. doi: 10.3389/fimmu.2024.1499301. eCollection 2024.
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Spatial transcriptomics: a new frontier in accurate localization of breast cancer diagnosis and treatment.空间转录组学:精准定位乳腺癌诊断和治疗的新前沿。
Front Immunol. 2024 Oct 8;15:1483595. doi: 10.3389/fimmu.2024.1483595. eCollection 2024.
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Single-cell and Spatial Transcriptomic Analyses Implicate Formation of the Immunosuppressive Microenvironment during Breast Tumor Progression.
单细胞和空间转录组分析表明,免疫抑制微环境在乳腺癌进展过程中的形成。
J Immunol. 2024 Nov 1;213(9):1392-1401. doi: 10.4049/jimmunol.2400025.
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Bin2cell reconstructs cells from high resolution Visium HD data.Bin2cell 从高分辨率 Visium HD 数据中重构细胞。
Bioinformatics. 2024 Sep 2;40(9). doi: 10.1093/bioinformatics/btae546.
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Eganelisib combined with immune checkpoint inhibitor therapy and chemotherapy in frontline metastatic triple-negative breast cancer triggers macrophage reprogramming, immune activation and extracellular matrix reorganization in the tumor microenvironment.依维莫司联合免疫检查点抑制剂治疗和化疗用于一线转移性三阴性乳腺癌可触发肿瘤微环境中巨噬细胞的重编程、免疫激活和细胞外基质重构。
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Integration of Bioinformatics and Machine Learning to Identify CD8+ T Cell-Related Prognostic Signature to Predict Clinical Outcomes and Treatment Response in Breast Cancer Patients.生物信息学和机器学习的整合,以识别 CD8+T 细胞相关的预后特征,预测乳腺癌患者的临床结局和治疗反应。
Genes (Basel). 2024 Aug 19;15(8):1093. doi: 10.3390/genes15081093.
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Intra-patient spatial comparison of non-metastatic and metastatic lymph nodes reveals the reduction of CD169 macrophages by metastatic breast cancers.原发灶内非转移性和转移性淋巴结的空间比较显示转移性乳腺癌导致 CD169 巨噬细胞减少。
EBioMedicine. 2024 Sep;107:105271. doi: 10.1016/j.ebiom.2024.105271. Epub 2024 Aug 21.
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Single-nucleus chromatin accessibility and transcriptomic map of breast tissues of women of diverse genetic ancestry.不同遗传血统女性乳腺组织的单核染色质可及性和转录组图谱。
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