Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
Exp Cell Res. 2023 Sep 15;430(2):113736. doi: 10.1016/j.yexcr.2023.113736. Epub 2023 Aug 2.
Endometrial cancer (EC) is an aggressive gynecological malignancy with an increased incidence rate. The immune landscape crucially affects immunotherapy efficacy and prognosis in EC patients. Here, we characterized the distinct tumor microenvironment signatures of EC tumors by analyzing single-cell RNA sequencing data from Gene Expression Omnibus and bulk RNA sequencing data from The Cancer Genome Atlas, which were compared with normal endometrium. Three macrophage subsets were identified, and two of them showed tissue-specific distribution. One of the macrophage subsets was dominant in macrophages derived from EC and exhibited characteristic behaviors such as promoting tumor growth and metastasis. One of the other macrophage subsets was mainly found in normal endometrium and served functions related to antigen presentation. We also identified a macrophage subset that was found in both EC and normal endometrial tissue. However, the pathway and cellular cross-talk of this subset were completely different based on the respective origin, suggesting a tumor-related differentiation mechanism of macrophages. Additionally, the tumor-enriched macrophage subset was found to predict immunotherapy responses in EC. Notably, we selected six genes from macrophage subset markers that could predict the survival of EC patients, SCL8A1, TXN, ANXA5, CST3, CD74 and NANS, and constructed a prognostic signature. To verify the signature, we identified immunohistochemistry for the tumor samples of 83 EC patients based on the selected genes and further followed up with the survival of the patients. Our results provide strong evidence that the signature can effectively predict the prognosis of EC patients.
子宫内膜癌（EC）是一种具有较高发病率的侵袭性妇科恶性肿瘤。免疫景观对 EC 患者的免疫治疗效果和预后有重要影响。在这里，我们通过分析来自基因表达综合数据库的单细胞 RNA 测序数据和来自癌症基因组图谱的批量 RNA 测序数据，对 EC 肿瘤的独特肿瘤微环境特征进行了表征，并将其与正常子宫内膜进行了比较。鉴定出三种巨噬细胞亚群，其中两种具有组织特异性分布。其中一种巨噬细胞亚群在源自 EC 的巨噬细胞中占主导地位，表现出促进肿瘤生长和转移的特征性行为。另一种巨噬细胞亚群主要存在于正常子宫内膜中，发挥与抗原呈递相关的功能。我们还鉴定出一种在 EC 和正常子宫内膜组织中均存在的巨噬细胞亚群。然而，根据各自的起源，该亚群的途径和细胞串扰是完全不同的，这表明巨噬细胞存在与肿瘤相关的分化机制。此外，富含肿瘤的巨噬细胞亚群被发现可预测 EC 中的免疫治疗反应。值得注意的是，我们从巨噬细胞亚群标志物中选择了六个可预测 EC 患者生存的基因，SCL8A1、TXN、ANXA5、CST3、CD74 和 NANS，并构建了一个预后特征。为了验证该特征，我们基于选定的基因对 83 名 EC 患者的肿瘤样本进行了免疫组织化学检测，并进一步对患者的生存情况进行了随访。我们的结果为该特征可有效预测 EC 患者的预后提供了有力证据。
