中国癌症防治杂志2025，Vol.17Issue(5)：627-639,13.DOI:10.3969/j.issn.1674-5671.2025.05.15
BEND3在乳腺癌中的多组学特征及其促增殖和转移作用研究
Multi-omics characteristics of BEND3 in breast cancer and its role in promoting prolifera-tion and metastasis
摘要
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 immu-nohistochemistry.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.关键词
乳腺癌/BEN结构域蛋白3/多组学/预后/增殖/转移Key words
Breast cancer/BEN domain containing 3/Multi-omics/Prognosis/Proliferation/Metastasis分类
医药卫生引用本文复制引用
张小燕,崔海燕,苟玉婷,李永祥,王仡阳,郭晨明..BEND3在乳腺癌中的多组学特征及其促增殖和转移作用研究[J].中国癌症防治杂志,2025,17(5):627-639,13.基金项目
国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) （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) （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) （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) （WKZX2023WK0109）
