Systematic pan-cancer analysis of tumour purity.

Systematic pan-cancer analysis of tumour purity.
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肿瘤纯度的系统泛滥分析。

DOI:
10.1038/ncomms9971
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发表时间:
2015-12-04
影响因子:
16.6
通讯作者:
Butte AJ
Butte AJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Aran D;Sirota M;Butte AJ

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肿瘤微环境是指肿瘤内和肿瘤周围存在的非肿瘤细胞,主要包括免疫细胞,但也包括成纤维细胞和构成支持血管的细胞。肿瘤的这些非癌成分可能在癌症生物学中发挥重要作用。它们对肿瘤样本的基因组分析也有很大的影响,并可能改变对结果的生物学解释。在这里,我们提出了一个系统的分析,使用不同的测量方式的肿瘤纯度的10,000个样本来自癌症基因组图谱21种癌症类型。根据临床特征对患者进行分层,试图检测由纯度水平驱动的临床差异。我们展示了肿瘤纯度对转录学数据与肿瘤的相关性和聚集性的混杂作用。最后,使用一种解释肿瘤纯度的差异表达方法,我们在几种癌症类型中发现了传统差异表达分析没有检测到的免疫治疗基因签名。肿瘤微环境的重要性现在已经被认识到了,然而,癌症样本中非肿瘤细胞的存在可能会使基因组分析复杂化。在这里,作者从TCGA数据集中估计了10,000个样本中的肿瘤纯度,并可以检测到T细胞激活的特征。
The tumour microenvironment is the non-cancerous cells present in and around a tumour, including mainly immune cells, but also fibroblasts and cells that comprise supporting blood vessels. These non-cancerous components of the tumour may play an important role in cancer biology. They also have a strong influence on the genomic analysis of tumour samples, and may alter the biological interpretation of results. Here we present a systematic analysis using different measurement modalities of tumour purity in >10,000 samples across 21 cancer types from the Cancer Genome Atlas. Patients are stratified according to clinical features in an attempt to detect clinical differences driven by purity levels. We demonstrate the confounding effect of tumour purity on correlating and clustering tumours with transcriptomics data. Finally, using a differential expression method that accounts for tumour purity, we find an immunotherapy gene signature in several cancer types that is not detected by traditional differential expression analyses. The importance of the tumour microenvironment has now been realised, however the presence of non-tumour cells in cancer samples can complicate genomic analyses. Here, the authors estimate tumour purity in 10,000 samples from the TCGA dataset and can detect a signature of T cell activation.