基于网络的泛癌免疫治疗反应转移指导乳腺癌预后。

IF 3.5 2区 生物学 Q1 MATHEMATICAL & COMPUTATIONAL BIOLOGY NPJ Systems Biology and Applications Pub Date : 2025-01-10 DOI:10.1038/s41540-024-00486-7
Xiaobao Ding, Lin Zhang, Ming Fan, Lihua Li
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引用次数: 0

摘要

乳腺癌预后因肿瘤异质性而复杂。传统的方法侧重于癌症特异性基因特征,但很少使用跨癌症策略来提供对肿瘤同质性的更深入的了解。免疫疗法,特别是免疫检查点抑制剂,在不同的癌症中产生不同的反应,提供了有价值的预后见解。我们引入了一种基于网络的泛癌免疫治疗反应转移(NBT),利用节点嵌入和热扩散算法,识别基因特征netNE和netHD,以提高乳腺癌预后。我们的研究结果显示,netHD和netNE在预后指标上优于7种已建立的乳腺癌特征,其中netHD表现优异。所有9个基因特征被分为3个簇,其中netHD和netNE富集了免疫相关的干扰素- γ通路。根据netHD将TCGA患者分为两组,发现50种癌症标志物中有20种存在显著的免疫学差异和变异,强调免疫相关标志物。这种方法利用泛癌症的见解来提高乳腺癌的预后,促进见解转移和提高肿瘤同质性的认识。基于网络的见解翻译泛癌症免疫治疗反应对乳腺癌预后的抽象图。这张抽象的图表说明了将免疫治疗反应从泛癌症研究转移到乳腺癌预后的概念框架。它强调了PPI网络的整合,以桥接遗传数据和临床表型。这种基于网络的方法通过利用免疫治疗反应信息,促进了乳腺癌预后基因特征的识别,为肿瘤同质性及其对临床结果的影响提供了新的视角。
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Network-based transfer of pan-cancer immunotherapy responses to guide breast cancer prognosis.

Breast cancer prognosis is complicated by tumor heterogeneity. Traditional methods focus on cancer-specific gene signatures, but cross-cancer strategies that provide deeper insights into tumor homogeneity are rarely used. Immunotherapy, particularly immune checkpoint inhibitors, results from variable responses across cancers, offering valuable prognostic insights. We introduced a network-based transfer (NBT) of pan-cancer immunotherapy responses to enhance breast cancer prognosis using node embedding and heat diffusion algorithms, identifying gene signatures netNE and netHD. Our results showed that netHD and netNE outperformed seven established breast cancer signatures in prognostic metrics, with netHD excelling. All nine gene signatures were grouped into three clusters, with netHD and netNE enriching the immune-related interferon-gamma pathway. Stratifying TCGA patients into two groups based on netHD revealed significant immunological differences and variations in 20 of 50 cancer hallmarks, emphasizing immune-related markers. This approach leverages pan-cancer insights to enhance breast cancer prognosis, facilitating insight transfer and improving tumor homogeneity understanding.Abstract graph of network-based insights translating pan-cancer immunotherapy responses to breast cancer prognosis. This abstract graph illustrates the conceptual framework for transferring immunotherapy response insights from pan-cancer studies to breast cancer prognosis. It highlights the integration of PPI networks to bridge genetic data and clinical phenotypes. The network-based method facilitates the identification of prognostic gene signatures in breast cancer by leveraging immunotherapy response information, providing a novel perspective on tumor homogeneity and its implications for clinical outcomes.

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来源期刊
NPJ Systems Biology and Applications
NPJ Systems Biology and Applications Mathematics-Applied Mathematics
CiteScore
5.80
自引率
0.00%
发文量
46
审稿时长
8 weeks
期刊介绍: npj Systems Biology and Applications is an online Open Access journal dedicated to publishing the premier research that takes a systems-oriented approach. The journal aims to provide a forum for the presentation of articles that help define this nascent field, as well as those that apply the advances to wider fields. We encourage studies that integrate, or aid the integration of, data, analyses and insight from molecules to organisms and broader systems. Important areas of interest include not only fundamental biological systems and drug discovery, but also applications to health, medical practice and implementation, big data, biotechnology, food science, human behaviour, broader biological systems and industrial applications of systems biology. We encourage all approaches, including network biology, application of control theory to biological systems, computational modelling and analysis, comprehensive and/or high-content measurements, theoretical, analytical and computational studies of system-level properties of biological systems and computational/software/data platforms enabling such studies.
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