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

IF 2.9 4区 医学 Q3 ENDOCRINOLOGY & METABOLISM
Juan Chen, Chang Zheng, Fei Zhang, Shiyao Sun, Guowen Liu, Guo Huang
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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.

基于alox15b的efferocysis簇:乳腺癌的预后意义和免疫细胞浸润。
目的:Efferocytosis是凋亡细胞清除的一个过程,与乳腺癌的发生和发展有关。本研究旨在构建efferocysis相关的遗传风险模型,以评估其在乳腺癌中的预后价值及其与免疫浸润的关系。方法:分析efferocyscs相关基因在乳腺癌组织中的表达规律,通过聚类分析探讨其与不同亚型肿瘤免疫浸润的关系。建立基于efferocyscs相关基因的风险模型,预测乳腺癌预后并评估其与免疫浸润的相关性。利用该模型,评估ALOX15B表达与乳腺癌生存之间的关系。在体外功能实验中,我们采用以下方法研究了ALOX15B在乳腺癌进展中的生物学作用:细胞增殖:采用MTT法、EdU结合法和集落形成法评估MCF7和MDA-MB-231细胞的增殖情况。Transwell用于量化迁移和入侵。流式细胞术观察细胞周期分布。Western blotting检测上皮-间质转化标志物的表达。结果:聚类分析efferocyscs相关基因在乳腺癌中的表达,A类预后良好,且与免疫细胞浸润密切相关。A簇中免疫应答激活和适应的功能富集分析可能是改善乳腺癌预后的重要因素。此外,构建了免疫相关基因风险模型,发现免疫相关基因是乳腺癌预后的有效预测因子。最后,强调ALOX15B的表达抑制乳腺癌细胞的增殖、运动、侵袭和DNA复制能力。ALOX15B也能抑制乳腺癌细胞的生长,在G1期阻滞细胞分裂。ALOX15B的表达与多种化疗药物的敏感性有关。结论:能胞饮相关模型可用于乳腺癌预后评估,而能胞饮相关基因ALOX15B可影响乳腺细胞的迁移和侵袭能力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Discover. Oncology
Discover. Oncology Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
2.40
自引率
9.10%
发文量
122
审稿时长
5 weeks
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