Coexpression analysis of large cancer datasets provides insight into the cellular phenotypes of the tumour microenvironment.
Coexpression analysis of large cancer datasets provides insight into the cellular phenotypes of the tumour microenvironment.
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DOI：
10.1186/1471-2164-14-469
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发表时间：
2013-07-11
期刊：
影响因子：
4.4
通讯作者：
Freeman TC
中科院分区：
文献类型：
--
作者：
Doig TN;Hume DA;Theocharidis T;Goodlad JR;Gregory CD;Freeman TC
由于癌症固有的异质性和样本收集的变幻性，从单个肿瘤中进行的活检在细胞组成方面表现出广泛的差异。因此，在转录组学分析中，在特定细胞类型中表达的基因或与某些生物过程相关的基因在不同样本中被检测到的水平变化很大。这种异质性也意味着在特定细胞类型或过程中特异性表达的基因的表达水平将随着样本中这些细胞的数量或途径的活性而变化，因此它们的表达是相关的。使用一种新颖的基于3D网络的方法，我们分析了来自1000多人的6个大型人类癌症微阵列数据集。基于这一分析，不需要分离单个细胞，我们已经定义了癌症表达数据中存在的广泛的细胞类型和通路特异性基因特征，这些特征也被发现在许多独立的数据集中很大程度上是保守的。肿瘤相关巨噬细胞的保守特征在很大程度上与肿瘤细胞类型无关。所有的基质细胞特征之间都有一定程度的相关性，因为它们都必须与肿瘤成分负相关。然而，在已建立的肿瘤的背景下，基质成分之间的相互作用似乎是多因素的，因为一种成分（如脉管系统）的水平与另一种成分（如巨噬细胞）的水平并不紧密相关。
Biopsies taken from individual tumours exhibit extensive differences in their cellular composition due to the inherent heterogeneity of cancers and vagaries of sample collection. As a result genes expressed in specific cell types, or associated with certain biological processes are detected at widely variable levels across samples in transcriptomic analyses. This heterogeneity also means that the level of expression of genes expressed specifically in a given cell type or process, will vary in line with the number of those cells within samples or activity of the pathway, and will therefore be correlated in their expression. Using a novel 3D network-based approach we have analysed six large human cancer microarray datasets derived from more than 1,000 individuals. Based upon this analysis, and without needing to isolate the individual cells, we have defined a broad spectrum of cell-type and pathway-specific gene signatures present in cancer expression data which were also found to be largely conserved in a number of independent datasets. The conserved signature of the tumour-associated macrophage is shown to be largely-independent of tumour cell type. All stromal cell signatures have some degree of correlation with each other, since they must all be inversely correlated with the tumour component. However, viewed in the context of established tumours, the interactions between stromal components appear to be multifactorial given the level of one component e.g. vasculature, does not correlate tightly with another, such as the macrophage.
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影响因子：
5.4
作者：
Freeman TC;Ivens A;Baillie JK;Beraldi D;Barnett MW;Dorward D;Downing A;Fairbairn L;Kapetanovic R;Raza S;Tomoiu A;Alberio R;Wu C;Su AI;Summers KM;Tuggle CK;Archibald AL;Hume DA
通讯作者：
Hume DA
影响因子：
20.3
作者：
Biswas, SK;Gangi, L;Sica, A
通讯作者：
Sica, A
影响因子：
64.8
作者：
Alizadeh, AA;Eisen, MB;Staudt, LM
通讯作者：
Staudt, LM
影响因子：
5.8
作者：
Chuang, Cheng-Long;Jen, Chih-Hung;Shieh, Grace S.
通讯作者：
Shieh, Grace S.
影响因子：
21.3
作者：
Asselin-Labat, Marie-Liesse;Sutherland, Kate D.;Visvader, Jane E.
通讯作者：
Visvader, Jane E.