Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Cancer Immunol Res. 2018 Jan;6(1):87-97. doi: 10.1158/2326-6066.CIR-17-0201. Epub 2017 Nov 15.
Surgical archives of tumor specimens are often impure. The presence of RNA transcripts from nontumor cells, such as immune and stromal cells, can impede analyses of cancer expression profiles. To systematically analyze the impact of tumor purity, the gene expression profiles and tumor purities were obtained for 7,794 tumor specimens across 21 tumor types (available in The Cancer Genome Atlas consortium). First, we observed that genes with roles in immunity and oxidative phosphorylation were significantly inversely correlated and correlated with the tumor purity, respectively. The expression of genes implicated in immunotherapy and specific immune cell genes, along with the abundance of immune cell infiltrates, was substantially inversely correlated with tumor purity. This relationship may explain the correlation between immune gene expression and mutation burden, highlighting the need to account for tumor purity in the evaluation of expression markers obtained from bulk tumor transcriptome data. Second, examination of cluster membership of gene pairs, with or without controlling for tumor purity, revealed that tumor purity may have a substantial impact on gene clustering across tumor types. Third, feature genes for molecular taxonomy were analyzed for correlation with tumor purity, and for some tumor types, feature genes representing the mesenchymal and classical subtypes were inversely correlated and correlated with tumor purity, respectively. Our findings indicate that tumor purity is an important confounder in evaluating the correlation between gene expression and clinicopathologic features such as mutation burden, as well as gene clustering and molecular taxonomy. .
肿瘤标本的手术档案通常是不纯的。非肿瘤细胞（如免疫细胞和基质细胞）的 RNA 转录本的存在会阻碍癌症表达谱的分析。为了系统地分析肿瘤纯度的影响，我们获得了 21 种肿瘤类型的 7794 个肿瘤标本的基因表达谱和肿瘤纯度（可在癌症基因组图谱联盟中获得）。首先，我们观察到在免疫和氧化磷酸化中起作用的基因分别与肿瘤纯度呈显著负相关和正相关。免疫治疗和特定免疫细胞基因表达的基因，以及免疫细胞浸润的丰度，与肿瘤纯度呈显著负相关。这种关系可能解释了免疫基因表达与突变负担之间的相关性，突出了在评估从批量肿瘤转录组数据中获得的表达标志物时需要考虑肿瘤纯度。其次，检查基因对的聚类成员，无论是否控制肿瘤纯度，都表明肿瘤纯度可能对跨肿瘤类型的基因聚类有重大影响。第三，分析了分子分类的特征基因与肿瘤纯度的相关性，对于一些肿瘤类型，代表间质和经典亚型的特征基因与肿瘤纯度呈负相关和正相关。我们的研究结果表明，肿瘤纯度是评估基因表达与突变负担等临床病理特征以及基因聚类和分子分类之间相关性的一个重要混杂因素。
