Epigenomic Deconvolution of Breast Tumors Reveals Metabolic Coupling between Constituent Cell Types.
Epigenomic Deconvolution of Breast Tumors Reveals Metabolic Coupling between Constituent Cell Types.
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DOI：
10.1016/j.celrep.2016.10.057
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发表时间：
2016-11-15
期刊：
影响因子：
8.8
通讯作者：
Milosavljevic A
中科院分区：
文献类型：
--
作者：
Onuchic V;Hartmaier RJ;Boone DN;Samuels ML;Patel RY;White WM;Garovic VD;Oesterreich S;Roth ME;Lee AV;Milosavljevic A
癌症进展取决于细胞内在过程和不同细胞类型之间的相互作用。然而，对肿瘤内单个细胞类型的细胞类型组成和分子谱进行大规模评估仍然具有挑战性。为了解决这个问题，我们开发了表观基因组解卷积 (EDec)，这是一种计算机方法，可以推断复杂组织的细胞类型组成以及组成细胞类型的 DNA 甲基化和基因转录谱。通过将 EDec 应用于癌症基因组图谱 (TCGA) 乳腺肿瘤，我们检测到与患者预后相关的免疫细胞浸润变化，以及乳腺癌亚型间质成纤维细胞与脂肪细胞比率的显着变化。我们进一步表明，脂肪基质较少往往表现出较低水平的线粒体活性，并且与氧化代谢水平较高的癌细胞相关。这些发现强调了基质成分在肿瘤内不同细胞类型之间的代谢耦合中的作用。奥努奇等人。开发一种计算机反卷积技术（EDec），可以准确估计乳腺肿瘤背景下的细胞类型组成和组成细胞类型的分子特征。将 TCGA 数据应用于乳腺癌揭示了基质成分与乳腺肿瘤代谢表型之间的关联。在 Cell Press IHEC 门户网站 www.cell.com/consortium/IHEC 上探索联盟数据。
Cancer progression depends on both cell-intrinsic processes and interactions between different cell types. However, large scale assessment of cell type composition and molecular profiles of individual cell types within tumors remains challenging. To address this, we developed Epigenomic Deconvolution (EDec), an in silico method that infers cell type composition of complex tissues as well as DNA methylation and gene transcription profiles of constituent cell types. By applying EDec to The Cancer Genome Atlas (TCGA) breast tumors we detect changes in immune cell infiltration related to patient prognosis, and a striking change in stromal fibroblast to adipocyte ratio across breast cancer subtypes. We further show that a less adipose stroma tends to display lower levels of mitochondrial activity and to be associated with cancerous cells with higher levels of oxidative metabolism. These findings highlight the role of stromal composition in the metabolic coupling between distinct cell types within tumors. Onuchic et al. develop an in silico deconvolution technique (EDec) that can accurately estimate cell type composition and molecular profiles of constituent cell types in the context of breast tumors. Application to breast cancers from TCGA data reveals association between stromal composition and the metabolic phonotype of breast tumors. Explore consortium data at the Cell Press IHEC webportal at www.cell.com/consortium/IHEC.
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影响因子：
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通讯作者：
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