Department of Obstetrics and Gynecology, Maternal and Child Health Care Hospital of Qinhuangdao, Qinhuangdao, China.
Department of Oncology, the First Hospital of Qinhuangdao City, Qinhuangdao, China.
Technol Cancer Res Treat. 2021 Jan-Dec;20:1533033821992083. doi: 10.1177/1533033821992083.
Estrogen-related receptor alpha (ESRRA) was reported to play an important role in multiple biological processes of neoplastic diseases. The roles of ESRRA in endometrial cancer have not been fully investigated yet.
Expression data and clinicopathological data of patients with uteri corpus endometrial carcinoma (UCEC) were obtained from The Cancer Genome Atlas (TCGA). Comprehensive bioinformatics analysis was performed, including receiver operating characteristics (ROC) curve analysis, Kaplan-Meier survival analysis, gene ontology (GO) enrichment analysis, and Gene Set Enrichment Analysis (GSEA). Immunohistochemistry was used to detect the protein expression level of ESRRA and CCK-8 assay was performed to evaluate the effect of ESRRA on the proliferation ability.
A total of 552 UCEC tissues and 35 normal tissues were obtained from the TCGA database. The mRNA and protein expression level of ESRRA was highly elevated in UCEC compared with normal tissues, and was closely associated with poor prognosis. ROC analysis indicated a very high diagnostic value of ESRRA for patients with UCEC. GO and GSEA functional analysis showed that ESRRA might be mainly involved in cellular metabolism processes, in turn, tumorigenesis and progression of UCEC. Knockdown of ESRRA inhibited the proliferation of UCEC cells in vitro. Further immune cell infiltration demonstrated that ESRRA enhanced the infiltration level of neutrophil cell and reduced that of T cell (CD4 naïve), NK cell, and cancer associated fibroblast (CAF). The alteration of immune microenvironment will greatly help in developing immune checkpoint therapy for UCEC.
Our study comprehensively analyzed the expression level, clinical value, and possible mechanisms of action of ESRRA in UCEC. These findings showed that ESRRA might be a potential diagnostic and therapeutic target.
雌激素相关受体α（ESRRA）被报道在多种肿瘤疾病的生物学过程中发挥重要作用。然而，ESRRA 在子宫内膜癌中的作用尚未被充分研究。
从癌症基因组图谱（TCGA）中获取了患有子宫体子宫内膜癌（UCEC）的患者的表达数据和临床病理数据。进行了综合的生物信息学分析，包括接收者操作特征（ROC）曲线分析、Kaplan-Meier 生存分析、基因本体（GO）富集分析和基因集富集分析（GSEA）。使用免疫组织化学检测 ESRRA 的蛋白表达水平，并用 CCK-8 测定法评估 ESRRA 对增殖能力的影响。
从 TCGA 数据库中获得了总共 552 例 UCEC 组织和 35 例正常组织。与正常组织相比，ESRRA 在 UCEC 中的 mRNA 和蛋白表达水平均显著升高，且与不良预后密切相关。ROC 分析表明，ESRRA 对 UCEC 患者具有非常高的诊断价值。GO 和 GSEA 功能分析表明，ESRRA 可能主要参与细胞代谢过程，进而影响 UCEC 的发生和发展。体外敲低 ESRRA 抑制了 UCEC 细胞的增殖。进一步的免疫细胞浸润表明，ESRRA 增强了中性粒细胞的浸润水平，降低了 T 细胞（CD4 幼稚）、NK 细胞和癌症相关成纤维细胞（CAF）的浸润水平。免疫微环境的改变将极大地有助于开发针对 UCEC 的免疫检查点治疗。
我们的研究全面分析了 ESRRA 在 UCEC 中的表达水平、临床价值和可能的作用机制。这些发现表明，ESRRA 可能是一个潜在的诊断和治疗靶点。
