Liu Yuexin
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Oncotarget. 2019 Mar 8;10(20):1993-2005. doi: 10.18632/oncotarget.26773.
Except for a few, the immune gene signatures for most cancer types are not available. We sought to identify a global immune gene signature that is applicable to all human cancers.
We identified an immune gene signature that was intimately correlated with tumor immune characteristics of human cancers and consisted of 382 genes indicative of different immune cell types. The T helper type 1 and 2 cell activation pathway was most significantly enriched in this global immune gene set, while transcription factors, such as SPI1 and STAT family members, were the top regulators of this gene signature. Skin cutaneous melanoma with higher expression of this immune gene signature had significantly longer survival than those with lower immune gene expression. Breast cancer patients with higher immune gene signature were significantly associated with advanced-stage.
We analyzed the gene expression profiles of 10,062 tumor samples from 32 cancer types in The Cancer Genome Atlas Pan-Cancer data set. Hierarchical clustering analysis of previously-defined immune genes was performed to identify a pan-cancer immune gene signature. Pathway and upstream regulator analyses were used to identify significantly enriched signaling pathways and transcription factors. Kaplan-Meier analysis was used to evaluate the survival difference between dichotomic groups with different immune gene signatures. Correlation of immune gene signature with tumor stage was also examined.
Our identified immune gene signature is applicable in human cancers and can be used to characterize tumor immunogenicity within and across cancer types. Clinical implication of this immune gene set warrants future investigation.
除少数癌症类型外，大多数癌症类型的免疫基因特征尚不明确。我们试图确定一种适用于所有人类癌症的全局免疫基因特征。
我们鉴定出一种与人类癌症的肿瘤免疫特征密切相关的免疫基因特征，它由382个指示不同免疫细胞类型的基因组成。1型和2型辅助性T细胞激活途径在这个全局免疫基因集中富集最为显著，而转录因子，如SPI1和STAT家族成员，是该基因特征的顶级调控因子。具有较高该免疫基因特征表达的皮肤黑色素瘤患者的生存期明显长于免疫基因表达较低的患者。免疫基因特征较高的乳腺癌患者与晚期显著相关。
我们分析了癌症基因组图谱泛癌数据集中来自32种癌症类型的10062个肿瘤样本的基因表达谱。对先前定义的免疫基因进行层次聚类分析，以确定泛癌免疫基因特征。采用通路和上游调控因子分析来鉴定显著富集的信号通路和转录因子。采用Kaplan-Meier分析评估具有不同免疫基因特征的二分群体之间的生存差异。还研究了免疫基因特征与肿瘤分期的相关性。
我们鉴定出的免疫基因特征适用于人类癌症，可用于描述癌症类型内部和之间的肿瘤免疫原性。该免疫基因集的临床意义值得未来进一步研究。
