基于炎症相关基因构建子宫内膜癌预后风险模型
收稿日期: 2025-02-08
修回日期: 2025-06-05
网络出版日期: 2025-06-06
基金资助
国家自然科学基金项目(82102850);吴阶平医学基金会临床科研专项基金项目(320.6750.2023.17-1);江苏省自然科学基金项目(BK20241993);江苏省卫生健康委医学科研重点项目(2024-36)
A prognostic risk model construction for endometrial cancer based on inflammation-related genes
Received date: 2025-02-08
Revised date: 2025-06-05
Online published: 2025-06-06
Supported by
National Natural Science Foundation of China(82102850);Wu Jieping Medical Foundation Special Fund for Clinical Research(320.6750.2023.17-1);Natural Science Foundation of Jiangsu Province, China(BK20241993);Key Medical Research Project of Jiangsu Provincial Health Commission(2024-36)
炎症反应参与多种肿瘤的发生与发展,影响肿瘤微环境,不仅促进肿瘤细胞的侵袭和迁移,同时也降低肿瘤治疗的敏感性。炎症被认为是子宫内膜癌(endometrial cancer,EC)发生发展的重要危险因素,但其影响EC发生发展的潜在机制尚不明确。本研究从癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库中获取EC患者RNA表达谱以及相关临床信息,利用生存分析及最小绝对值收缩和选择算子算法(least absolute shrinkage and selection operator,LASSO)筛选出关键炎症相关基因(inflammation-related genes,IRG),构建了包含9条非零系数IRG的预后风险评分模型及列线图预测模型。生存分析显示,低风险组患者生存率更高,预后更佳。通过测试集和校正曲线验证两个模型均具有良好的预测性能。然后,从基因表达综合数据库(Gene Expression Omnibus,GEO)中获取EC相关数据集,作为外部验证进一步确认模型的可靠性。接着,通过免疫浸润分析发现高低风险组在9种免疫细胞间具有显著差异,多种免疫细胞与肿瘤的进展及预后相关。同时药物敏感性分析发现1种EC代表性药物他莫昔芬与上述IRG之一存在显著相关关系。综上所述,本研究成功构建了EC风险评分模型和列线图预测模型,有望能更好地预测EC患者总生存期并提供新的治疗靶点。
刘鉴瑶, 李越, 胡缓缓, 肖姝玥, 谢欣怡, 钟山亮, 贡震, 朱晨静, 徐寒子 . 基于炎症相关基因构建子宫内膜癌预后风险模型[J]. 遗传, 2025 , 47(9) : 1007 -1022 . DOI: 10.16288/j.yczz.24-376
Inflammatory responses have been identified as a critical factor in the development and progression of various types of tumors. These responses influence the tumor microenvironment, promoting tumor cell invasion and migration while concomitantly reducing the efficacy of tumor therapy. Inflammation is widely regarded as a significant risk factor for the development of endometrial cancer (EC). However, the precise mechanisms through which it influences the development of EC remain to be elucidated. In this study, we obtain RNA expression profiles of EC patients and related clinical information from The Cancer Genome Atlas (TCGA) database. We then screen key inflammation-related genes using survival analysis and the least absolute value shrinkage and selection operator (LASSO) algorithms. Based on this, we finally construct a prognostic risk scoring model containing nine non-zero coefficient IRGs and an alignment diagram prediction model. Survival analysis demonstrates that patients in the low-risk group exhibit a higher survival rate and more favorable prognosis. The predictive performance of both models was confirmed through the analysis of test sets and calibration curves. Subsequently, we obtain EC-related datasets from the Gene Expression Omnibus (GEO) database to serve as an external validation, thereby further substantiating the reliability of the models. Subsequent immune infiltration analysis revealed significant disparities among nine immune cell types between the high- and low-risk groups, with multiple immune cells correlating with tumor progression and prognosis. Concurrently, we perform drug sensitivity analysis, it reveals a significant correlation between one representative EC drug, tamoxifen, and one of the aforementioned IRGs. In summary, our study successfully constructs a risk score model and a column-line graph prediction model for EC. It is expected that these models will better predict the overall survival and provide new therapeutic targets for EC patients.
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