Immune response characterization of endometrial cancer.
Immune response characterization of endometrial cancer.
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DOI：
10.18632/oncotarget.26630
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发表时间：
2019-01-29
期刊：
影响因子：
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通讯作者：
Liu, Yuexin
中科院分区：
文献类型：
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作者：
Liu, Yuexin
背景：免疫激活在子宫内膜癌中的综合特征和预后相关性尚不清楚。结果：我们系统地报道了一组子宫内膜样癌，其特征是多方面的免疫特征，如肿瘤纯度低，白细胞比例高，显著的CD8淋巴细胞浸润和抗肿瘤效果，并显著上调免疫抑制基因标记物。我们还发现，表达与更好的生存相关的基因在免疫相关的信号通路中显著丰富，这表明肿瘤浸润性淋巴细胞在子宫内膜癌中具有良好的预后。此外，我们发现免疫细胞在这类肿瘤中的募集可能是由于STAT1信号网络的转录激活。方法：我们从公开可用的数据库中获得多维基因组数据，并将其与我们最近在子宫内膜癌中发现的四种基于基因表达的亚型相关联。上游调控因子分析用于确定最显着丰富的转录调控因子，独创性途径分析用于确定生存相关基因中信号通路的丰富。对200个基因的T细胞肿瘤浸润性基因特征进行基因集浓缩分析，比较第四簇和其他三个簇的组合。所有的统计检验都是双侧的，在所进行的所有分析中，P值小于0.05被认为是显著的。结论：这项研究有助于识别免疫激活的患者，他们可能受益于新出现的免疫检查点抑制剂。
BACKGROUND: The comprehensive characterization and prognostic relevance of immune activation in endometrial cancer remain largely unknown.RESULTS: We systematically reported a subset of endometrioid-type endometrial cancer characterized by multifaceted immune features such as low tumor purity, high leukocyte percentage, and striking CD8 lymphocytic infiltration with anti-tumor efficacy along with marked upregulation of immunosuppressive gene markers. We also showed that genes whose expression was significantly correlated with better survival were significantly enriched in the immune-related signaling pathways, suggesting that tumor-infiltrating lymphocytes give rise to a favorable prognosis in endometrial cancer. Furthermore, we showed that immune cell recruitment in this subset of tumors is likely due to the transcriptional activation of the STAT1 signaling network.METHODS: We obtained the multi-dimensional genomic data from publicly available databases and correlated them with the four gene expression-based subtypes we recently identified in endometrial cancer. Upstream regulator analysis was used to identify the most significantly enriched transcription regulators and Ingenuity pathway analysis was applied to determine enrichment of signaling pathways in survival-associated genes. Gene set enrichment analysis was performed on the 200-gene T-cell tumor infiltration gene signature comparing Cluster IV with the other three clusters combined. All statistical tests were two-sided, and a P value of less than 0.05 is considered significant across all analyses performed.CONCLUSION: This study helps to identify patients with immune activation who are likely to benefit from emerging immune checkpoint inhibitors.