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中国癌症防治杂志

中国癌症防治杂志 ›› 2025, Vol. 17 ›› Issue (5): 627-339.doi: 10.3969/j.issn.1674-5671.2025.05.15

• 论著 • 上一篇    下一篇

 BEND3在乳腺癌中的多组学特征及其促增殖和转移作用研究

  

  1. 新疆医科大学第一附属医院消化血管外科中心乳腺外科；巴音郭楞蒙古自治州人民医院甲乳外科
  • 出版日期:2025-10-25 发布日期:2025-12-03
  • 通讯作者: 郭晨明 E-mail:gcm_xjmu@yeah.net
  • 基金资助:
    家自然科学基金项目（82560576；32260186）；省部共建中亚高发病成因与防治国家重点实验室项目（SKL?HIDCA?2024?21）；新疆维吾尔自治区自然科学基金杰出青年科学基金项目（2024D01E22）；青年科技拔尖人才项目——青年科技创新人才培养“天山英才”（2022TSYCCX0029）；国家卫生健康委医药卫生科技发展研究中心“外科规范化诊疗研究”项目（WKZX2023WK0109）

Multi-omics characteristics of BEND3 in breast cancer and its role in promoting proliferation and metastasis

  • Online:2025-10-25 Published:2025-12-03

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摘要： 目的 探讨BEN结构域蛋白3（BEN domain containing 3，BEND3）在乳腺癌中的多组学特征及其对肿瘤细胞增殖、迁移、侵袭的影响。方法 基于TCGA、GTEx、GEO、UALCAN和HPA数据库分析BEND3 mRNA及蛋白质表达的差异和预后价值。采集2023年8月至2024年7月期间新疆医科大学第一附属医院手术切除的48对乳腺癌及癌旁组织样本进行免疫组织化学检测。使用单因素和多因素Cox回归以及Kaplan⁃Meier生存分析评估预后意义，并通过PrognoScan和Kaplan⁃Meier Plotter工具进行验证。利用cBioPortal和GSCA平台分析基因突变、拷贝数变异及甲基化水平。采用TIMER2.0分析免疫细胞浸润情况，STRING构建蛋白互作（protein⁃protein interaction，PPI）网络，随后进行GO、KEGG和GSEA富集分析。通过qRT⁃PCR和Western blot验证BEND3在乳腺癌细胞系MCF⁃7和MDA⁃MB⁃231中的敲低与过表达效果。分别采用CCK⁃8法、克隆形成实验、划痕实验和Transwell实验检测细胞的增殖、迁移、侵袭能力。结果 BEND3的mRNA和蛋白质水平在乳腺癌中均显著升高（P<0.001），尤其在Basal型和三阴型中表达升高（均P<0.001）。BEND3对BRCA检测具有中等诊断价值（AUC=0.820），BEND3高表达与较短总生存期、疾病特异性生存期、无进展间隔期相关（P<0.05），且为乳腺癌患者总生存期的独立危险因素（P=0.030）。BEND3表达受基因扩增、拷贝数变异以及DNA、RNA甲基化调控，与免疫细胞浸润、肿瘤突变负荷及新抗原水平相关。功能富集分析显示其参与调控细胞周期、Notch通路及代谢重编程等信号通路。体外实验表明，BEND3过表达促进乳腺癌细胞增殖、迁移和侵袭，敲低则抑制这些效应（均P<0.05）。结论 BEND3在乳腺癌中显著过表达，受遗传变异及表观遗传改变的调控，与不良预后和肿瘤免疫微环境相关。BEND3的高表达可促进乳腺癌细胞增殖、迁移和侵袭。

关键词: 乳腺癌, BEN结构域蛋白3, 多组学, 预后, 增殖, 转移

Abstract: Objective To investigate the multi⁃omics characteristics of BEN domain containing 3(BEND3 ) in breast cancer and its effect on tumor cell proliferation, migration, and invasion. Methods BEND3 mRNA and protein expression were analyzed for prognostic value using the TCGA, GTEx, and GEO, UALCAN and HPA database, A total of 48 paired breast cancer and adjacent tissues samples from The First Affiliated Hospital of Xinjiang Medical University (August 2023 to July 2024) were collected for immunohistochemistry. Prognostic significance was assessed with univariable and multivariable Cox regression and Kaplan⁃Meier analyses, validated by PrognoScan and Kaplan⁃Meier Plotter. Genetic mutations, copy number variations, and methylation status were examined using the cBioPortal and GSCA. Immune cell infiltration was assessed via TIMER2.0, and a protein⁃protein interaction (PPI) network was constructed using STRING, followed by GO, KEGG, and GSEA enrichment analyses. BEND3 knockdown and overexpression in MCF⁃7 and MDA⁃MB⁃231 cell lines were verified by qRT⁃PCR and Western blot. Subsequently, cell proliferation, migration, and invasion were evaluated using CCK⁃8 assay, clolny formation assay wound healing assay, and Transwell assays, respectively. Results BEND3 mRNA and protein levels were significantly elevated in breast cancer (P<0.001), particularly in the Basal and triple⁃negative subtypes (all P<0.001). It exhibited moderate diagnostic value for breast cancer (AUC=0.820) and was linked to poor  overall survival, disease⁃specific survival and progression⁃free interval (all P<0.05), serving as an independent prognostic risk factor for breast cancer (P<0.05). BEND3 expression was influenced by gene amplification, copy number variation, and DNA and RNA methylation, and was correlated with immune cell infiltration, tumor mutational burden and neoantigen load. Functional enrichment analysis revealed that it was involved in cell cycle and Notch signaling, as well as metabolic reprogramming. In vitro, BEND3 overexpression enhanced breast cancer cell proliferation, migration, and invasion, while knockdown inhibited these effects (all P<0.05). Conclusions BEND3 is markedly overexpressed in  breast cancer and is modulated by genetic and epigenetic alterations, associated with poor prognosis and the tumor immune microenvironment. The elevated expression of BEND3 facilitates the proliferation, migration, and invasion in  breast cancer cell.

Key words: Breast cancer, BEN domain containing 3, Multi?omics, Prognosis, Proliferation, Metastasis

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