Department of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
J Immunol. 2022 Oct 15;209(8):1606-1614. doi: 10.4049/jimmunol.2200329. Epub 2022 Sep 12.
Some patients with endometrial cancer (EC) suffer from limited survival benefits after immunotherapy, suggesting that there may be a specific pattern associated with immunotherapy. Immune-related genes were extracted from The Cancer Genome Atlas databases. We analyzed the differences among immune subtypes (ISs) in the distribution of the tumor mutational burden, chemotherapy-induced immune response markers, immune checkpoint-related genes, immunotherapy, and chemotherapy. We applied dimensionality reduction and defined the immune landscape of EC. Then, we used the Weighted Gene Co-Expression Network Analysis package to identify the coexpression modules of these immune genes. Finally, hub genes were selected and detected by quantitative PCR and immunohistochemistry. We obtained three ISs. There were differences in the distribution of the tumor mutational burden, chemotherapy-induced immune response markers, and immune checkpoint-related genes among the ISs. Regarding immunotherapy and chemotherapy, the IS2 subtypes were more sensitive to programmed cell death protein 1 inhibitors. In addition, different positions in the immune landscape map exhibited different prognostic characteristics, providing further evidence of the ISs. The IS2 subtypes were significantly positively correlated with yellow module gene list, indicating a good prognosis with high score. SIRPG and SLAMF1 were identified as the final characteristic genes. The quantitative PCR and immunohistochemistry results showed that the expression levels of SIRPG and SLAMF1 were low in human EC tissue. In this study, we identified three reproducible ISs of EC. The immune landscape analysis further revealed the intraclass heterogeneity of the ISs. SIRPG and SLAMF1 were identified to be associated with progression, suggesting that they may be novel immune-related biomarkers of EC.
一些子宫内膜癌（EC）患者在免疫治疗后获益有限，这表明可能存在与免疫治疗相关的特定模式。从癌症基因组图谱数据库中提取免疫相关基因。我们分析了免疫亚型（ISs）在肿瘤突变负担、化疗诱导的免疫反应标志物、免疫检查点相关基因、免疫治疗和化疗分布方面的差异。我们应用降维方法定义了 EC 的免疫景观。然后，我们使用加权基因共表达网络分析包识别这些免疫基因的共表达模块。最后，通过定量 PCR 和免疫组织化学检测选择和检测枢纽基因。我们获得了三个 ISs。在肿瘤突变负担、化疗诱导的免疫反应标志物和免疫检查点相关基因的分布方面，ISs 之间存在差异。关于免疫治疗和化疗，IS2 亚型对程序性细胞死亡蛋白 1 抑制剂更敏感。此外，免疫景观图中的不同位置表现出不同的预后特征，为 ISs 提供了进一步的证据。IS2 亚型与黄色模块基因列表呈显著正相关，表明高评分具有良好的预后。SIRPG 和 SLAMF1 被确定为最终的特征基因。定量 PCR 和免疫组织化学结果表明，SIRPG 和 SLAMF1 在人 EC 组织中的表达水平较低。在这项研究中，我们确定了 EC 的三个可重复的 ISs。免疫景观分析进一步揭示了 ISs 的类内异质性。SIRPG 和 SLAMF1 被确定与进展相关，表明它们可能是 EC 的新型免疫相关生物标志物。
