Ding Xiaobao, Zhang Lin, Fan Ming, Li Lihua
Institute of Biomedical Engineering and Instrumentation, Hangzhou Dianzi University, Hangzhou, China.
Institute of Big Data and Artificial Intelligence in Medicine, School of Electronics and Information Engineering, Taizhou University, Taizhou, China.
NPJ Syst Biol Appl. 2025 Jan 10;11(1):4. doi: 10.1038/s41540-024-00486-7.
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.
肿瘤异质性使乳腺癌的预后变得复杂。传统方法侧重于癌症特异性基因特征,但能更深入洞察肿瘤同质性的跨癌症策略却很少被使用。免疫疗法,尤其是免疫检查点抑制剂,在不同癌症中的反应各不相同,能提供有价值的预后见解。我们引入了一种基于网络的泛癌免疫疗法反应转移(NBT)方法,利用节点嵌入和热扩散算法来改善乳腺癌预后,识别出基因特征netNE和netHD。我们的结果表明,在预后指标方面,netHD和netNE优于七种已确立的乳腺癌特征,其中netHD表现更出色。所有九种基因特征被分为三个簇,netHD和netNE富集了与免疫相关的干扰素-γ途径。根据netHD将TCGA患者分为两组,发现50个癌症特征中有20个存在显著的免疫差异和变化,突出了免疫相关标志物。这种方法利用泛癌见解来改善乳腺癌预后,促进见解转移并增进对肿瘤同质性的理解。基于网络的见解将泛癌免疫疗法反应转化为乳腺癌预后的抽象图。此抽象图展示了将免疫疗法反应见解从泛癌研究转移到乳腺癌预后的概念框架。它强调了蛋白质-蛋白质相互作用(PPI)网络的整合,以连接遗传数据和临床表型。基于网络的方法通过利用免疫疗法反应信息,有助于识别乳腺癌中的预后基因特征,为肿瘤同质性及其对临床结果的影响提供了新的视角。