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基于ALOX15B的胞葬作用簇:乳腺癌中的预后意义及免疫细胞浸润

ALOX15B-based efferocytosis clusters: prognostic implications and immune cell infiltration in breast cancer.

作者信息

Chen Juan, Zheng Chang, Zhang Fei, Sun Shiyao, Liu Guowen, Huang Guo

机构信息

Department of Oncology, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, Cancer Institute, Xinhua Hospital, Peking University Shenzhen Hospital, Shenzhen, 518036, China.

Department of Thyroid and Breast Surgery, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, Guangdong, China.

出版信息

Discov Oncol. 2025 Jun 19;16(1):1159. doi: 10.1007/s12672-025-02961-x.

Abstract

OBJECTIVE

Efferocytosis, a process of apoptotic cell clearance, is implicated in the initiation and progression of breast cancer. This study aims to construct an efferocytosis-related genetic risk model to evaluate its prognostic value and its association with immune infiltration in breast cancer.

METHODS

The expression patterns of efferocytosis-related genes in breast cancer were analyzed, followed by clustering analysis to explore their relationship with tumor immune infiltration across different subtypes. A risk model based on efferocytosis-related genes was developed to predict breast cancer prognosis and assess its correlation with immune infiltration. Using this model, the association between ALOX15B expression and breast cancer survival was evaluated. In Vitro Functional Assays, the biological role of ALOX15B in breast cancer progression was investigated using the following approaches: Cellular Proliferation: MTT assay, EdU incorporation assay, and colony formation assay were performed to assess proliferation in MCF7 and MDA-MB-231 cells. Transwell was used to quantify migratory and invasive. Flow cytometry was conducted to evaluate cell cycle distribution. Western blotting was performed to assess Epithelial-Mesenchymal Transition marker expression.

RESULTS

Clustering analysis of the expression of efferocytosis-related genes in breast cancer, Cluster A had a good prognosis and was closely associated with immune cell infiltration. Functional enrichment analysis of the activation and adaptation of immune response in Cluster A clustering may be an important factor in improving breast cancer prognosis. In addition, an immune-related gene risk model was constructed, which was found to be a valid predictor of breast cancer prognosis. Finally, it was highlighted that the expression of ALOX15B inhibited the proliferation, movement, invasion, and DNA replication capability of breast cancer cells. The growth of breast cancer cells was also impeded by ALOX15B, which hindered cell division during the G1 phase. The expression of ALOX15B is associated with the sensitivity of a variety of chemotherapeutic agents.

CONCLUSION

Efferocytosis-related models can be used for the assessment of breast cancer prognosis, while the efferocytosis-related gene ALOX15B can affect the migration and invasive ability of breast cells.

摘要

目的

胞葬作用是一种凋亡细胞清除过程,与乳腺癌的发生和发展有关。本研究旨在构建一个与胞葬作用相关的遗传风险模型,以评估其预后价值及其与乳腺癌免疫浸润的关系。

方法

分析乳腺癌中与胞葬作用相关基因的表达模式,随后进行聚类分析,以探讨它们与不同亚型肿瘤免疫浸润的关系。开发了一种基于与胞葬作用相关基因的风险模型,以预测乳腺癌预后并评估其与免疫浸润的相关性。使用该模型,评估了ALOX15B表达与乳腺癌生存之间的关联。体外功能试验,采用以下方法研究ALOX15B在乳腺癌进展中的生物学作用:细胞增殖:进行MTT试验、EdU掺入试验和集落形成试验,以评估MCF7和MDA-MB-231细胞的增殖情况。使用Transwell定量迁移和侵袭能力。进行流式细胞术以评估细胞周期分布。进行蛋白质印迹法以评估上皮-间质转化标志物的表达。

结果

对乳腺癌中与胞葬作用相关基因的表达进行聚类分析,A簇预后良好,且与免疫细胞浸润密切相关。对A簇中免疫反应的激活和适应进行功能富集分析,可能是改善乳腺癌预后的重要因素。此外,构建了一个免疫相关基因风险模型,发现它是乳腺癌预后的有效预测指标。最后,强调ALOX15B的表达抑制了乳腺癌细胞的增殖、运动、侵袭和DNA复制能力。ALOX15B还阻碍了乳腺癌细胞的生长,在G1期阻碍细胞分裂。ALOX15B的表达与多种化疗药物的敏感性相关。

结论

与胞葬作用相关的模型可用于评估乳腺癌预后,而与胞葬作用相关的基因ALOX15B可影响乳腺细胞的迁移和侵袭能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db92/12179036/65b3e08ec2b1/12672_2025_2961_Fig1_HTML.jpg

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