BCHE 作为子宫内膜癌的预后生物标志物及其与免疫的相关性。
BCHE as a Prognostic Biomarker in Endometrial Cancer and Its Correlation with Immunity.
机构信息
Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
出版信息
J Immunol Res. 2022 Jul 21;2022:6051092. doi: 10.1155/2022/6051092. eCollection 2022.
BACKGROUND
In developed countries, the most common gynecologic malignancy is endometrial carcinoma (EC), making the identification of EC biomarkers extremely essential. As a natural enzyme, butyrylcholinesterase (BCHE) is found in hepatocytes and plasma. There is a strong correlation between BCHE gene mutations and cancers and other diseases. The aim of this study was to analyze the role of BCHE in patients with EC.
METHODS
A variety of analyses were conducted on The Cancer Genome Atlas (TCGA) data, including differential expression analysis, enrichment analysis, immunity, clinicopathology, and survival analysis. The Gene Expression Omnibus (GEO) database was used to validate outcomes. Using R tools, Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) analyses revealed the potential mechanisms of BCHE in EC. Sangerbox tools were used to delve into the relations between BCHE expression and tumor microenvironment, including microsatellite instability (MSI), tumor neoantigen count (TNC), and tumor mutation burden (TMB). BCHE's genetic alteration analysis was conducted by cBioPortal. In addition, the Human Protein Atlas (HPA) was used to validate the outcomes by immunohistochemistry, and an analysis of the protein-protein interaction network (PPI) was performed with the help of the STRING database.
RESULTS
Based on our results, BCHE was a significant independent prognostic factor for patients with EC. The prognosis with EC was affected by age, stage, grade, histological type, and BCHE. GSEA showed that BCHE was closely related to pathways regulating immune response, including transforming growth factor- (TGF-) signaling pathways and cancer immunotherapy through PD1 blockade pathways. The immune analysis revealed that CD4+ regulatory T cells (Tregs) were negatively correlated with BCHE expression and the immune checkpoint molecules CD28, ADORA2A, BTNL2, and TNFRSF18 were all significantly related to BCHE. BCHE expression was also associated with TMB by genetic alteration analysis.
CONCLUSIONS
Identifying BCHE as a biomarker for EC might help predict its prognosis and could have important implications for immunotherapy.
背景
在发达国家，最常见的妇科恶性肿瘤是子宫内膜癌（EC），因此识别 EC 的生物标志物极其重要。作为一种天然酶，丁酰胆碱酯酶（BCHE）存在于肝细胞和血浆中。BCHE 基因突变与癌症和其他疾病之间存在很强的相关性。本研究旨在分析 BCHE 在 EC 患者中的作用。
方法
对 The Cancer Genome Atlas（TCGA）数据库进行了多种分析，包括差异表达分析、富集分析、免疫、临床病理和生存分析。使用 Gene Expression Omnibus（GEO）数据库验证结果。使用 R 工具进行基因集富集分析（GSEA）和基因本体论（GO）分析，揭示了 BCHE 在 EC 中的潜在机制。使用 Sangerbox 工具深入研究了 BCHE 表达与肿瘤微环境之间的关系，包括微卫星不稳定性（MSI）、肿瘤新抗原计数（TNC）和肿瘤突变负荷（TMB）。通过 cBioPortal 进行 BCHE 的遗传改变分析。此外，使用 Human Protein Atlas（HPA）通过免疫组化验证结果，并借助 STRING 数据库进行蛋白质-蛋白质相互作用网络（PPI）分析。
结果
根据我们的结果，BCHE 是 EC 患者的一个重要独立预后因素。EC 的预后受年龄、分期、分级、组织学类型和 BCHE 影响。GSEA 显示 BCHE 与调节免疫反应的途径密切相关，包括转化生长因子-（TGF-）信号通路和通过 PD1 阻断途径的癌症免疫治疗。免疫分析显示 CD4+调节性 T 细胞（Tregs）与 BCHE 表达呈负相关，免疫检查点分子 CD28、ADORA2A、BTNL2 和 TNFRSF18 均与 BCHE 显著相关。通过遗传改变分析，BCHE 表达还与 TMB 相关。
结论
将 BCHE 鉴定为 EC 的生物标志物可能有助于预测其预后，并可能对免疫治疗具有重要意义。
Zotero 插件