Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries and its prevalence is increasing. As an emerging therapy with a promising efficacy, immunotherapy has been extensively applied in the treatment of solid tumors. In addition, chromatin regulators (CRs), as essential upstream regulators of epigenetics, play a significant role in tumorigenesis and cancer development. CRs and immune checkpoint-related genes (ICRGs) were obtained from the previous top research. The Genome Cancer Atlas (TCGA) was utilized to acquire the mRNA expression and clinical information of patients with EC. Correlation analysis was utilized for screen CRs-related ICRGs (CRRICRGs). By Cox regression and least absolute shrinkage and selection operator (LASSO) analysis, prognosis related CRRICRGs were screened out and risk model was constructed. The Kaplan–Meier curve was used to estimate the prognosis between high- and low-risk group. By comparing the IC50 value, the drugs sensitivity difference was explored. We obtained small molecule drugs for the treatment of UCEC patients based on CAMP dataset. We successfully constructed a 9 CRRICRs-based prognostic signature for patients with UCEC and found the riskscore was an independent prognostic factor. The results of functional analysis suggested that CRRICRGs may be involved in immune processes associated with cancer. Immune characteristics analysis provided further evidence that the CRRICRGs-based model was correlated with immune cells infiltration and immune checkpoint. Eight small molecule drugs that may be effective for the treatment of UCEC patients were screened. Effective drugs identified by drug sensitivity profiling in high- and low-risk groups. In summary, our study provided novel insights into the function of CRRICRGs in UCEC. We also developed a reliable prognostic panel for the survival of patients with UCEC.

中文翻译：

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一种新的染色质调节剂相关免疫检查点相关基因预后特征和子宫内膜癌患者的潜在候选药物

子宫内膜癌（EC）是发达国家最常见的妇科恶性肿瘤，其患病率呈上升趋势。免疫疗法作为一种具有良好疗效的新兴疗法，已广泛应用于实体瘤的治疗。此外，染色质调节因子（CRs）作为表观遗传学的重要上游调节因子，在肿瘤发生和癌症发展中发挥着重要作用。CRs和免疫检查点相关基因（ICRGs）是从之前的顶级研究中获得的。利用基因组癌症图谱 (TCGA) 获取 EC 患者的 mRNA 表达和临床信息。相关分析用于筛选 CRs 相关的 ICRGs (CRRICRGs)。通过Cox回归和最小绝对收缩和选择算子（LASSO）分析，筛选出与预后相关的CRRICRGs并构建风险模型。Kaplan-Meier 曲线用于评估高危组和低危组之间的预后。通过比较IC50值，探讨药物敏感性差异。我们基于 CAMP 数据集获得了用于治疗 UCEC 患者的小分子药物。我们成功地为 UCEC 患者构建了 9 个基于 CRRICRs 的预后特征，发现风险评分是一个独立的预后因素。功能分析结果表明 CRRICRGs 可能参与与癌症相关的免疫过程。免疫特征分析进一步证明基于 CRRICRGs 的模型与免疫细胞浸润和免疫检查点相关。筛选了八种可能对治疗UCEC患者有效的小分子药物。通过对高风险和低风险人群的药物敏感性分析确定的有效药物。总之，我们的研究为 CRRICRGs 在 UCEC 中的功能提供了新的见解。我们还为 UCEC 患者的生存开发了一个可靠的预后小组。