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乳腺癌干细胞景观特征分析及干性相关预后基因特征的鉴定以辅助免疫治疗

Characterization of stem cell landscape and identification of stemness-relevant prognostic gene signature to aid immunotherapy in breast cancer.

作者信息

Yang Xiaozhou, Yang Xiaojun, Tang Haili, Chen Xin, Wang Jiangang, Zhao Huadong

机构信息

Department of General Surgery, The Second Affiliated Hospital of the Air Force Medical University, Xi'an, 710038, China.

出版信息

Discov Oncol. 2025 Jan 5;16(1):9. doi: 10.1007/s12672-025-01742-w.

Abstract

A common digestive system cancer with a dismal prognosis and a high death rate globally is breast cancer (BRCA). BRCA recurrence, metastasis, and medication resistance are all significantly impacted by cancer stem cells (CSCs). However, the relationship between CSCs and the tumor microenvironment in BRCA individuals remains unknown, and this information is critically needed. Our research utilized bioinformatics techniques and TCGA data to explore the complex relationship between CSCs and BRCA development. We identified 26 stem cell gene sets from the Stem Checker database and classified BRCA samples into stemness subtypes using consensus clustering. Prognosis, tumor microenvironment (TME) elements, and treatment responses varied across subtypes. Using LASSO, Cox regression, and differential expression analysis, we developed a stemness-risk model. BRCA patients were divided into two groups (Cluster A and Cluster B). Cluster B exhibited an improved prognosis, higher PIK3CA mutation frequency, and increased levels of CD8 T cells and regulatory Tregs. A 5-gene stemness model was constructed, showing that higher stemness scores correlated with poorer prognosis. The model was validated using the METABRIC cohort data from cBioPortal. Our findings identify two stemness-related subgroups with distinct prognoses and TME patterns. Further experimental validation is necessary before this model can be considered for clinical application.

摘要

乳腺癌(BRCA)是一种常见的消化系统癌症,在全球范围内预后不佳且死亡率高。癌症干细胞(CSCs)对BRCA的复发、转移和耐药性均有显著影响。然而,BRCA患者中CSCs与肿瘤微环境之间的关系尚不清楚,而这一信息至关重要。我们的研究利用生物信息学技术和TCGA数据来探索CSCs与BRCA发生发展之间的复杂关系。我们从Stem Checker数据库中鉴定出26个干细胞基因集,并使用一致性聚类将BRCA样本分类为干性亚型。不同亚型的预后、肿瘤微环境(TME)要素和治疗反应各不相同。通过LASSO、Cox回归和差异表达分析,我们构建了一个干性风险模型。BRCA患者被分为两组(A组和B组)。B组预后改善,PIK3CA突变频率更高,CD8 T细胞和调节性Tregs水平升高。构建了一个5基因干性模型,结果显示较高的干性评分与较差的预后相关。该模型使用来自cBioPortal的METABRIC队列数据进行了验证。我们的研究结果确定了两个与干性相关的亚组,它们具有不同的预后和TME模式。在该模型可考虑用于临床应用之前,还需要进一步的实验验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6117/11700959/6a967237163c/12672_2025_1742_Fig1_HTML.jpg

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