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鉴定与乳腺癌预后和免疫浸润相关的外泌体特征。

Identification of an exosome-related signature associated with prognosis and immune infiltration in breast cancer.

机构信息

Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.

Stem Cell Laboratory, Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China.

出版信息

Sci Rep. 2023 Oct 24;13(1):18198. doi: 10.1038/s41598-023-45325-7.

Abstract

Exosomes, nanosized vesicles, play a vital role in breast cancer (BC) occurrence, development, and drug resistance. Hence, we proceeded to study the potential prognostic value of exosome-related genes and their relationship to the immune microenvironment in BC. 121 exosome-related genes were provided by the ExoBCD database, and 7 final genes were selected to construct the prognostic signature. Besides, the expression levels of the 7 exosome-related genes were validated by the experiment in BC cell lines. Based on the signature, BC patients from the training and validation cohorts were separated into low- and high-risk groups. Subsequently, the R clusterProfiler package was applied to identify the distinct enrichment pathways between high-risk groups and low-risk groups. The relevance of the tumor immune microenvironment and exosome-related gene risk score were analyzed in BC. Eventually, the different expression levels of immune checkpoint-related genes were compared between the two risk groups. Based on the risk model, the low-risk groups were identified with a higher survival rate both in the training and validation cohorts. A better overall survival was revealed in patients with higher scores evaluated by the estimation of stromal and immune cells in malignant tumor tissues using expression (ESTIMATE) algorithm. Subsequently, BC patients with lower risk scores were indicated by higher expression levels of some immune checkpoint-related genes and immune cell infiltration. Exosomes are closely associated with the prognosis and immune cell infiltration of BC. These findings may contribute to improving immunotherapy and provide a new vision for BC treatment strategies.

摘要

外泌体是纳米大小的囊泡,在乳腺癌(BC)的发生、发展和耐药中起着至关重要的作用。因此,我们着手研究外泌体相关基因在乳腺癌中的潜在预后价值及其与免疫微环境的关系。ExoBCD 数据库提供了 121 个外泌体相关基因,最终选择了 7 个基因来构建预后特征。此外,通过 BC 细胞系的实验验证了这 7 个外泌体相关基因的表达水平。基于该特征,来自训练集和验证集的 BC 患者被分为低风险组和高风险组。随后,应用 R 聚类分析包来识别高风险组和低风险组之间明显的富集途径。分析了 BC 中肿瘤免疫微环境与外泌体相关基因风险评分的相关性。最后,比较了两个风险组之间免疫检查点相关基因的不同表达水平。基于风险模型,在训练集和验证集中,低风险组的生存率均较高。通过使用表达(ESTIMATE)算法评估恶性肿瘤组织中基质和免疫细胞,发现高评分患者的总体生存率更高。随后,通过一些免疫检查点相关基因和免疫细胞浸润的高表达,表明低风险组的 BC 患者具有更好的预后。外泌体与 BC 的预后和免疫细胞浸润密切相关。这些发现可能有助于改善免疫治疗,并为 BC 治疗策略提供新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef48/10598067/db8f064cb7e3/41598_2023_45325_Fig1_HTML.jpg

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