Low tumor purity is associated with poor prognosis, heavy mutation burden, and intense immune phenotype in colon cancer.
Low tumor purity is associated with poor prognosis, heavy mutation burden, and intense immune phenotype in colon cancer.
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低肿瘤纯度与结肠癌的不良预后、重突变负担和强烈的免疫表型相关
DOI：
10.2147/cmar.s171855
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发表时间：
2018
影响因子：
3.3
通讯作者：
Xu J
中科院分区：
文献类型：
--
作者：
Mao Y;Feng Q;Zheng P;Yang L;Liu T;Xu Y;Zhu D;Chang W;Ji M;Ren L;Wei Y;He G;Xu J
肿瘤纯度定义为肿瘤组织中癌细胞的比例。肿瘤纯度对结肠癌 (CC) 预后、遗传图谱和微环境的影响尚未得到彻底了解。回顾性收集来自三个公共数据集 GSE17536/17537、GSE39582 和 TCGA 的临床和转录组数据 (n=1,248)。通过基于转录组数据的计算方法推断每个样品的肿瘤纯度。对包含 GSE17536/17537 和 GSE39582 (n=794) 的微阵列数据集进行生存相关分析，而 TCGA 数据集用于后续基因组分析 (n=454)。右侧 CC 患者的肿瘤纯度明显较低。低纯度 CC 的生存率较差，肿瘤纯度被确定为独立的预后因素。此外，肿瘤纯度高的CC患者从辅助化疗中获益更多。随后的基因组分析发现，突变负荷与肿瘤纯度呈负相关，只有 APC 和 KRAS 在高纯度 CC 中突变明显较多。然而，体细胞拷贝数改变事件与肿瘤纯度无关。此外，免疫相关途径和免疫治疗相关标记（程序性细胞死亡蛋白 1 [PD-1]、程序性死亡配体 1 [PD-L1]、细胞毒性 T 淋巴细胞相关蛋白 4 [CTLA-4]、淋巴细胞激活基因 3 [LAG-3] 以及 T 细胞免疫球蛋白和粘蛋白结构域 含有-3 [TIM-3]）在低纯度样品中高度富集。值得注意的是，M2 巨噬细胞和中性粒细胞的相对比例与肿瘤纯度呈负相关，这表明 CC 中的生存率较差。肿瘤纯度对于 CC 预后分层以及辅助化疗获益预测具有潜在价值。低纯度 CC 中相对较差的存活率可能归因于关键途径中较高的突变频率和与纯度相关的微环境变化。
Tumor purity is defined as the proportion of cancer cells in the tumor tissue. The impact of tumor purity on colon cancer (CC) prognosis, genetic profile, and microenvironment has not been thoroughly accessed. Clinical and transcriptomic data from three public datasets, GSE17536/17537, GSE39582, and TCGA, were retrospectively collected (n=1,248). Tumor purity of each sample was inferred by a computational method based on transcriptomic data. Survival-related analyses were performed on microarray dataset containing GSE17536/17537 and GSE39582 (n=794), whereas TCGA dataset was utilized for subsequent genomic analysis (n=454). Right-sided CC patients showed a significantly lower tumor purity. Low purity CC conferred worse survival, and tumor purity was identified as an independent prognostic factor. Moreover, high tumor purity CC patients benefited more from adjuvant chemotherapy. Subsequent genomic analysis found that the mutation burden was negatively associated with tumor purity, with only APC and KRAS significantly more mutated in high purity CC. However, no somatic copy number alteration event was correlated with tumor purity. Furthermore, immune-related pathways and immunotherapy-associated markers (programmed cell death protein 1 [PD-1], programmed death-ligand 1 [PD-L1], cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], Lymphocyte-activation gene 3 [LAG-3] and T-cell immunoglobulin and mucin-domain containing-3 [TIM-3]) were highly enriched in low purity samples. Notably, the relative proportion of M2 macrophages and neutrophils, which indicated worse survival in CC, was negatively associated with tumor purity. Tumor purity exhibited potential value for CC prognostic stratification as well as adjuvant chemotherapy benefit prediction. The relative worse survival in low purity CC may attribute to higher mutation frequency in key pathways and purity-related microenvironmental changing.