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基于干性的特征签名,通过机器学习揭示了其在鉴别子宫内膜癌患者预后、免疫反应和体细胞突变方面的显著作用。

A stemness-based signature with inspiring indications in discriminating the prognosis, immune response, and somatic mutation of endometrial cancer patients revealed by machine learning.

机构信息

Gynecology Department 2, Cangzhou Central Hospital, Cangzhou, Hebei, China.

Second Department of Anesthesia, Cangzhou Central Hospital, Cangzhou, Hebei, China.

出版信息

Aging (Albany NY). 2024 Jul 30;16(14):11248-11274. doi: 10.18632/aging.205979.

DOI:10.18632/aging.205979
PMID:39079132
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11315399/
Abstract

Endometrial cancer (EC) is a fatal gynecologic tumor. Bioinformatic tools are increasingly developed to screen out molecular targets related to EC. Our study aimed to identify stemness-related prognostic biomarkers for new therapeutic strategies in EC. In this study, we explored the prognostic value of cancer stem cells (CSCs), characterized by self-renewal and unlimited proliferation, and its correlation with immune infiltrates in EC. Transcriptome and somatic mutation profiles of EC were downloaded from TCGA database. Based on their stemness signature and DEGs, EC patients were divided into two subtypes via consensus clustering, and patients in Stemness Subtype I presented significantly better OS and DFS than Stemness Subtype II. Subtype I also displayed better clinicopathological features, and genomic variations demonstrated different somatic mutation from subtype II. Additionally, two stemness subtypes had distinct tumor immune microenvironment patterns. In the end, three machine learning algorithms were applied to construct a 7-gene stemness subtype risk model, which were further validated in an external independent EC cohort in our hospital. This novel stemness-based classification could provide a promising prognostic predictor for EC and may guide physicians in selecting potential responders for preferential use of immunotherapy. This novel stemness-dependent classification method has high value in predicting the prognosis, and also provides a reference for clinicians in selecting sensitive immunotherapy methods for EC patients.

摘要

子宫内膜癌(EC)是一种致命的妇科肿瘤。生物信息学工具的不断发展,有助于筛选出与 EC 相关的分子靶标。我们的研究旨在确定与 EC 新治疗策略相关的干性相关预后生物标志物。在这项研究中,我们探索了癌症干细胞(CSCs)的预后价值,CSCs 的特征是自我更新和无限增殖,并研究了其与 EC 中免疫浸润的相关性。从 TCGA 数据库中下载了 EC 的转录组和体细胞突变谱。基于其干性特征和 DEGs,通过共识聚类将 EC 患者分为两个亚型,Stemness Subtype I 组的 OS 和 DFS 明显优于 Stemness Subtype II 组。Stemness Subtype I 组还表现出更好的临床病理特征,基因组变异与 subtype II 存在不同的体细胞突变。此外,两种干性亚型具有不同的肿瘤免疫微环境模式。最后,应用三种机器学习算法构建了一个 7 基因干性亚型风险模型,并在我院的另一个 EC 外部独立队列中进行了验证。这种基于干性的新型分类方法可为 EC 提供有前途的预后预测指标,并可能指导医生为潜在的免疫治疗反应者选择优先使用免疫治疗的方法。这种基于干性的分类方法在预测预后方面具有很高的价值,也为临床医生选择 EC 患者敏感的免疫治疗方法提供了参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d41/11315399/aec09a6273d8/aging-16-205979-g007.jpg
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