This study investigates the influence of aging‐related genes on endometrial cancer, a prominent gynecological malignancy with rising incidence and mortality. By analyzing gene expression differences between cancerous and normal endometrial tissues, 42 aging‐related genes were identified as differentially expressed. Utilizing the TCGA‐UCEC sample, consensus clustering divided the samples into two molecular subgroups, Aging low and Aging high, based on their expression profiles. These subgroups showed distinct prognoses and survival rates, with the Aging high group associated with DNA repair and cell cycle pathways, and the Aging low group showing suppressed metabolic pathways and increased immune cell infiltration, suggesting a potential for better immunotherapy outcomes. Mutation analysis did not find significant differences in mutation frequencies between the groups, but a high Tumor Mutation Burden (TMB) correlated with better prognosis. A risk score model was also developed, showcasing significant prognostic power. Further analysis of the SIX1 gene revealed its overexpression in cancer cells. Drug sensitivity tests indicated that the low‐risk group might respond better to chemotherapy. This research underscores the significance of aging‐related genes in endometrial cancer, offering insights into their prognostic value and therapeutic potential, which could lead to personalized treatment approaches and enhanced patient management.

中文翻译：

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子宫内膜癌中年龄相关基因的毒理学预后意义研究揭示患者预后的关键因素

本研究调查了衰老相关基因对子宫内膜癌的影响，子宫内膜癌是一种发病率和死亡率不断上升的重要妇科恶性肿瘤。通过分析癌性子宫内膜组织和正常子宫内膜组织之间的基因表达差异，发现 42 个与衰老相关的基因存在差异表达。利用 TCGA-UCEC 样本，共识聚类根据样本的表达谱将样本分为两个分子亚组：Aging low 和 Aging high。这些亚组显示出不同的预后和存活率，其中衰老高组与 DNA 修复和细胞周期途径相关，而衰老低组则显示出代谢途径受到抑制和免疫细胞浸润增加，这表明免疫治疗结果有可能更好。突变分析没有发现各组之间的突变频率存在显着差异，但高肿瘤突变负担（TMB）与更好的预后相关。还开发了风险评分模型，显示出显着的预后能力。对 SIX1 基因的进一步分析揭示了它在癌细胞中的过度表达。药物敏感性测试表明低风险组可能对化疗反应更好。这项研究强调了衰老相关基因在子宫内膜癌中的重要性，提供了对其预后价值和治疗潜力的见解，这可能导致个性化治疗方法和加强患者管理。