Luo Guoxian, Bo Caiying, Li Jianqi
Department of Gynecology, The Fourth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Department of Obstetrics and Gynecology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Medicine (Baltimore). 2025 May 2;104(18):e42338. doi: 10.1097/MD.0000000000042338.
Uterine corpus endometrioid carcinoma (UCEC) is a prevalent malignant tumor of the female reproductive system. Despite advancements in molecular biology and treatment strategies, the underlying molecular mechanisms of UCEC tumorigenesis remain incompletely understood. This study aimed to identify differentially expressed genes (DEGs) associated with UCEC pathogenesis, and to determine potential prognostic biomarkers and immunotherapy targets for UCEC. RNA expression datasets and clinical data from UCEC patients were collected from the UCSC Xena database and The Cancer Genome Atlas database. Principal component analysis and LIMMA methods were employed to screen 177 UCEC tissues and 24 normal endometrial tissues. Gene ontology enrichment analysis revealed that up-regulated DEGs were primarily involved in tissue development, cell cycle regulation, and epithelial development. Subsequently, weighted gene co-expression network analysis (WGCNA) identified DEGs in the blue modules that were significantly positively correlated with UCEC, while DEGs in the black modules were significantly negatively correlated with UCEC. Among the identified DEGs through WGCNA, 16 genes were selected, and further Kaplan-Meier analysis demonstrated that 5 of these genes (AURKA, CCNE1, IQGAP3, TTK, and UBE2C) were significantly negatively correlated with overall survival (OS) and considered as hub genes. The expression of these hub genes was validated using GEO datasets and immunohistochemistry (IHC) analysis from the human protein atlas. Additionally, the calculation of immune scores for immune infiltration, immune cell infiltration, and immune cell regulation across the 5 hub genes revealed potential immunotherapeutic targets and strategies. This comprehensive investigation provides insights into the molecular mechanisms underlying UCEC development, identifies 5 promising prognostic biomarkers and immunotherapy targets, and offers guidance for UCEC treatment approaches.
子宫内膜样癌（UCEC）是女性生殖系统中一种常见的恶性肿瘤。尽管分子生物学和治疗策略取得了进展，但UCEC肿瘤发生的潜在分子机制仍未完全明确。本研究旨在鉴定与UCEC发病机制相关的差异表达基因（DEGs），并确定UCEC潜在的预后生物标志物和免疫治疗靶点。从UCSC Xena数据库和癌症基因组图谱数据库收集了UCEC患者的RNA表达数据集和临床数据。采用主成分分析和LIMMA方法筛选了177例UCEC组织和24例正常子宫内膜组织。基因本体富集分析显示，上调的DEGs主要参与组织发育、细胞周期调控和上皮发育。随后，加权基因共表达网络分析（WGCNA）确定蓝色模块中的DEGs与UCEC显著正相关，而黑色模块中的DEGs与UCEC显著负相关。在通过WGCNA鉴定出的DEGs中，选择了16个基因，进一步的Kaplan-Meier分析表明，其中5个基因（AURKA、CCNE1、IQGAP3、TTK和UBE2C）与总生存期（OS）显著负相关，并被视为枢纽基因。使用GEO数据集和人类蛋白质图谱的免疫组织化学（IHC）分析验证了这些枢纽基因的表达。此外，通过计算这5个枢纽基因的免疫浸润、免疫细胞浸润和免疫细胞调节的免疫评分，揭示了潜在的免疫治疗靶点和策略。这项全面的研究深入了解了UCEC发展的分子机制，确定了5个有前景的预后生物标志物和免疫治疗靶点，并为UCEC的治疗方法提供了指导。
