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淋巴结阳性luminal型乳腺癌腋窝治疗反应和肿瘤微环境改变的多组学预测

Multi-omics prediction of axillary treatment response and tumour microenvironment alterations in lymph node-positive luminal breast cancer.

作者信息

Ma Teng, Wang Zirui, Zhou Zhe, Wang Yongmei, Ma Tianyi, Liu Xiangping, Mao Yan, Wang Haibo

机构信息

Breast Disease Center, Affiliated Hospital of Qingdao University, Qingdao, 266000, China.

Zhongtai Securities Institute for Financial Studies, Shandong University, Jinan, 250100, China.

出版信息

Cell Death Dis. 2025 Aug 4;16(1):588. doi: 10.1038/s41419-025-07877-6.

DOI:10.1038/s41419-025-07877-6
PMID:40759637
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12322124/
Abstract

Luminal breast cancer (BC) with axillary lymph node (ALN) metastasis is typically treated with neoadjuvant chemotherapy (NAC). Theoretically, patients who achieve pathological lymph node complete response after NAC can be exempted from ALN dissection and even have the possibility of being spared axillary surgery. However, there is no effective way to preoperatively assess whether a metastatic ALN achieved pathological lymph node complete response (pLCR) after NAC. Therefore, we retrospectively collected imaging, clinical, and pathological data from two centres, built a multi-omic model to predict pLCR, and validated its accuracy and clinical applicability. We identified 12 radiomic and four clinicopathological features for model construction; the areas under the curve for training and validation cohorts were 0.853 and 0.805, respectively. Subsequently, single-cell RNA sequencing analysis was conducted on patients with different efficacy and its association with the tumour immune microenvironment was investigated. Eleven cell clusters in 14 samples from five patients were identified with differing NAC responses; comparative analysis indicated that those with poor responses had immunosuppressive features, which provided a theoretical basis for elucidating the resistance mechanism of NAC in axillary metastatic lymph nodes. The multi-omics prediction model demonstrated good performance in predicting ALN status after NAC, offering the possibility of reducing unnecessary axillary surgery.

摘要

伴有腋窝淋巴结转移的腔面型乳腺癌通常采用新辅助化疗(NAC)进行治疗。理论上,在接受NAC治疗后达到病理淋巴结完全缓解的患者可以免于腋窝淋巴结清扫,甚至有可能避免腋窝手术。然而,目前尚无有效的方法在术前评估转移性腋窝淋巴结在接受NAC治疗后是否达到病理淋巴结完全缓解(pLCR)。因此,我们回顾性收集了两个中心的影像学、临床和病理数据,构建了一个多组学模型来预测pLCR,并验证了其准确性和临床适用性。我们确定了12个放射组学特征和4个临床病理特征用于模型构建;训练队列和验证队列的曲线下面积分别为0.853和0.805。随后,对不同疗效的患者进行了单细胞RNA测序分析,并研究了其与肿瘤免疫微环境的关联。在来自5例患者的14个样本中鉴定出11个细胞簇,其对NAC的反应不同;比较分析表明,反应较差的细胞簇具有免疫抑制特征,这为阐明腋窝转移性淋巴结中NAC的耐药机制提供了理论依据。多组学预测模型在预测NAC治疗后的腋窝淋巴结状态方面表现良好,为减少不必要的腋窝手术提供了可能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6936/12322124/6b6556677118/41419_2025_7877_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6936/12322124/6815a28536f6/41419_2025_7877_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6936/12322124/6b6556677118/41419_2025_7877_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6936/12322124/dd883eee144c/41419_2025_7877_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6936/12322124/e0431b9bb030/41419_2025_7877_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6936/12322124/752c2bd6e5ec/41419_2025_7877_Fig3_HTML.jpg
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Chinese Society of Clinical Oncology (CSCO) Breast Cancer guidelines 2024.中国临床肿瘤学会(CSCO)乳腺癌诊疗指南2024
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