Lu Shan, Wei Yiyun, Chen Liuyan, Cheng Jinlian, Qin Liuyan, Lu Xuemei, Pang Lihong
Department of Prenatal Diagnosis and Genetic Disease Diagnosis, The First Affliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Department of Obstetrics and Gynecology, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, China.
Sci Rep. 2025 Jul 1;15(1):22165. doi: 10.1038/s41598-025-06672-9.
Endometrial cancer (EC) is one of the few malignancies with increasing incidence and mortality rates. Targeted therapy and immunotherapy have become pivotal treatment strategies for EC patients. However, the current methods and biomarkers for predicting immunotherapy responses and prognosis are remain limited. Programmed cell death (PCD) pathways play a crucial role in cancer development and progression and may serve as prognostic markers and indicators of drug sensitivity in EC. In our study, we integrated multiple PCD pathways and comprehensive multi-omics datasets from TCGA-EC and GEO databases. By analyzing distinct PCD signatures, we discovered two major EC subgroups with distinctive prognoses, tumor microenvironment (TME) profiles, and responses to immunotherapy. To further investigate the cellular basis of these PCD patterns, single-cell RNA sequencing analysis was conducted to explore tumor heterogeneity in PCD characteristics across EC subpopulations. Further investigation revealed seven key PCD-associated genes (HIF3A, ACTL8, SIRPG, FBN3, ARHGAP30, CD6, and P2RY13) that formed the basis for a novel prognostic scoring system-risk score (RS). Our findings showed that patients with lower risk scores had better survival rates and improved immunotherapy outcomes. Conversely, patients with higher risk scores experienced poor clinical outcomes and reduced immunotherapy efficacy, although alternative therapies such as docetaxel and olaparib demonstrated potential therapeutic benefits. Overall, the RS provides a valuable tool for early prognosis prediction and for identifying patients who may benefit from immunotherapy.
子宫内膜癌（EC）是少数发病率和死亡率呈上升趋势的恶性肿瘤之一。靶向治疗和免疫治疗已成为EC患者的关键治疗策略。然而，目前预测免疫治疗反应和预后的方法及生物标志物仍然有限。程序性细胞死亡（PCD）途径在癌症的发生和发展中起着关键作用，可能作为EC的预后标志物和药物敏感性指标。在我们的研究中，我们整合了来自TCGA-EC和GEO数据库的多个PCD途径和综合多组学数据集。通过分析不同的PCD特征，我们发现了两个主要的EC亚组，它们具有不同的预后、肿瘤微环境（TME）特征和对免疫治疗的反应。为了进一步研究这些PCD模式的细胞基础，我们进行了单细胞RNA测序分析，以探索EC亚群中PCD特征的肿瘤异质性。进一步研究发现了七个关键的PCD相关基因（HIF3A、ACTL8、SIRPG、FBN3、ARHGAP30、CD6和P2RY13），它们构成了一种新的预后评分系统——风险评分（RS）的基础。我们的研究结果表明，风险评分较低的患者生存率更高，免疫治疗效果更好。相反，风险评分较高的患者临床结局较差，免疫治疗疗效降低，尽管多西他赛和奥拉帕尼等替代疗法显示出潜在的治疗益处。总体而言，RS为早期预后预测和识别可能从免疫治疗中获益的患者提供了一个有价值的工具。
