Co-expression modules identified from published immune signatures reveal five distinct immune subtypes in breast cancer
Co-expression modules identified from published immune signatures reveal five distinct immune subtypes in breast cancer
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DOI：
10.1007/s10549-016-4041-3
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发表时间：
2017-01-01
影响因子：
3.8
通讯作者：
Yau, Christina
中科院分区：
文献类型：
--
作者：
Amara, Dominic;Wolf, Denise M.;Yau, Christina
越来越多的文献表明，免疫相关表达特征可以预测乳腺癌预后和化疗/靶向治疗反应。然而，尚不清楚这些特征是否相互关联或代表不同的免疫相关信号。我们评估了四个公共乳腺癌数据集中总计 3295 个样本的 57 个已发表的免疫相关表达特征。对于每个数据集，我们使用共识聚类根据签名的共表达模式将其分组在一起。所有四个数据集的同一共识簇中的签名用于定义免疫模块。然后使用共识聚类根据肿瘤的模块评分将肿瘤分为免疫亚型。使用 Cox 比例风险模型进行生存分析。共识聚类在整个数据集中一致产生四个不同的共表达模块。这些模块似乎代表了不同的免疫成分和信号，其中成分特征涉及 (1) T 细胞和/或 B 细胞 (T/B-cell)、(2) 干扰素 (IFN)、(3) 转化生长因子 β (TGFB) 和 (4) 核心血清反应、树突状细胞和/或巨噬细胞 (CSR)。基于这些共表达模块的肿瘤亚型一致产生属于五种主要免疫亚型的子集：T/B细胞/IFN高、IFN/CSR高、CSR高、TGFB高和免疫低。与 T/B 细胞/IFN 高亚型肿瘤患者相比，患有 CSR 高肿瘤的基底和/或三阴性乳腺癌患者的预后明显较差。我们的探索性研究从已发表的免疫特征中识别出四种不同的免疫共表达模块（T/B 细胞、IFN、TGFB 或 CSR）。使用这些模块，我们确定了五种在基底乳腺癌中具有显着结果差异的免疫亚型。
There is a growing body of literature demonstrating that immune-related expression signatures predict breast cancer prognosis and chemo-/targeted-therapy responsiveness. However, it is unclear whether these signatures correlate with each other or represent distinct immune-related signals.We evaluated 57 published immune-related expression signatures in four public breast cancer datasets totaling 3295 samples. For each dataset, we used consensus clustering to group signatures together based on their co-expression pattern. Signatures that were in the same consensus cluster across all four datasets were used to define immune modules. Tumors were then classified into immune subtypes based on their module scores using consensus clustering. Survival analysis was conducted using Cox proportional hazards modeling.Consensus clustering consistently yields four distinct co-expression modules across the datasets. These modules appear to represent distinct immune components and signals, where constituent signatures relate to (1) T-cells and/or B-cells (T/B-cell), (2) interferon (IFN), (3) transforming growth factor beta (TGFB), and (4) core-serum response, dendritic cells, and/or macrophages (CSR). Subtyping of tumors based on these co-expression modules consistently yields subsets that fall into five major immune subtypes: T/B-cell/IFN High, IFN/CSR High, CSR High, TGFB High, and Immune Low. Basal and/or triple-negative breast cancer patients with CSR High tumors have significantly worse outcome relative to those within the T/B-cell/IFN High subtype.Our exploratory study identified four distinct immune co-expression modules (T/B-cell, IFN, TGFB, or CSR) from published immune signatures. Using these modules, we identified five immune subtypes with significant outcome differences in basal breast cancers.