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目的 通过生物信息学技术分析三阴性乳腺癌(triple-negative breast cancer, TNBC)进展过程中关键基因的作用。方法 在国家生物技术信息中心(national center for biotechnology information, NCBI)-高通量基因表达数据库(gene expression omnibus, GEO)中下载GSE65194、GSE38959和GSE81838共3组TNBC基因芯片表达谱。使用GEO2R分析正常乳腺组织与TNBC组织的表达差异，筛选出每个基因芯片表达谱的差异表达基因(differentially expressed genes, DEGs)。使用Venn软件取交集，并对交集DEGs进行基因本体分析(gene ontology analysis, GO)和京都基因与基因组百科全书分析(kyoto encyclopedia of genes and genomes, KEGG)。通过STRING数据库构建交集DEGs的蛋白质相互作用网络，并利用cytoHubba插件筛选出hub基因。通过GEPIA2数据库验证hub基因表达水平，结合UALCAN数据库生存分析筛选出预后相关基因KIF4A,并验证其与乳腺癌临床分期的关联性，随后，进一步通过GEPIA2数据库分析其在TNBC与其他乳腺癌亚型的表达差异。结果 3组乳腺癌数据集(GSE81838、GSE38959、GSE65194)共获得197个共有DEGs。GO功能分析显示，交集DEGs涉及的分子功能(molecular function, MF)包括微管结合等通路；在生物过程(biological processes, BP)中，主要作用于细胞器分裂等通路；在细胞组分(cellular component, CC)中主要集中在染色体区域等通路。KEGG通路分析显示，交集DEGs主要富集在细胞周期、马达蛋白等。通过蛋白互作网络鉴定出19个hub基因，其中驱动蛋白家族成员4A(kinesin family member 4A,KIF4A)与患者预后显著相关。同时KIF4A的表达与乳腺癌的临床分期紧密关联，且在TNBC中KIF4A表达量的中位数显著高于管腔型和HER2阳性亚型。结论 KIF4A在TNBC组织中显著高表达，表达水平与患者临床预后密切相关，提示KIF4A有望成为潜在的分子标志物和治疗干预靶点。
Abstract：Objective The role of key genes in the progression of triple-negative breast cancer(TNBC) was analyzed by bioinformatics techniques.Methods A total of three sets of TNBC gene chip expression profiles, GSE65194,GSE38959 and GSE81838,were downloaded from the NCBI-GEO database.The expression differences between normal breast tissues and TNBC tissues were analyzed using GEO2R,and the differentially expressed genes(DEGs) of each gene chip expression profile were screened out.Intersections were taken using Venn software, and gene ontology analysis(GO) and kyoto encyclopedia of genes and genomes(KEGG) were performed on the intersected DEGs.Protein interaction networks of intersecting DEGs were constructed by the STRING database, and hub genes were screened using the cytoHubba plug-in.The expression level of hub gene was verified by GEPIA2 database, and the prognosis-related gene KIF4A was screened by combining with the survival analysis of UALCAN database, and its association with the clinical stage of breast cancer was verified, and subsequently, its expression difference between TNBC and other breast cancer subtypes was further analyzed by GEPIA2 database.Results A total of 197 shared DEGs were obtained from the three breast cancer datasets(GSE81838,GSE38959,and GSE65194).GO functional analysis showed that the intersecting DEGs were involved in molecular functions(MF),including pathways such as microtubule binding; and in biological processes(BP),they mainly act in pathways such as organelle division; in cellular component(CC),they mainly focus on pathways such as chromosome region, etc.KEGG pathway analysis showed that the intersecting DEGs were mainly enriched in cell cycle, motor proteins and so on.Nineteen hub genes were identified by protein interaction network, among which kinesin family member 4A(KIF4A) was significantly associated with patient prognosis.Meanwhile, the expression of KIF4A was closely associated with the clinical stage of breast cancer, and the median expression of KIF4A was significantly higher in TNBC than in luminal and HER2-positive subtypes.Conclusion KIF4A was highly expressed in TNBC tissues, and the expression level was closely related to the clinical prognosis of patients, suggesting that KIF4A is expected to be a potential molecular marker and target for therapeutic intervention.
[1] Smolarz B,Nowak AZ,Romanowicz H.Breast cancer-epidemiology,classification,pathogenesis and treatment(review of literature) [J].Cancers(Basel),2022,14(10):2569.
[2] Ma L,Song G,Li M,et al.Construction and comprehensive analysis of a cerna network to reveal potential novel biomarkers for triple-negative breast cancer[J].Cancer Manag Res,2020,12:7061-7075.
[3] Satam H,Joshi K,Mangrolia U,et al.Next-generation sequencing technology:current trends and advancements[J].Biology(Basel),2023,12(7):997.
[4] Adrada BE,Moseley TW,Kapoor MM,et al.Triple-negative breast cancer:histopathologic features,genomics,and treatment[J].Radiographics,2023,43(10):e230034.
[5] Li J,Chen L,Tan W,et al.Platinum is essential in neoadjuvant treatment of triple-negative breast cancer:a network meta-analysis[J].Cancer Biol Med,2022,19(5):742-754.
[6] Obidiro O,Battogtokh G,Akala EO.Triple negative breast cancer treatment options and limitations:future outlook[J].Pharmaceutics,2023,15(7):1796.
[7] Zhao K,Li X,Feng Y,et al.The role of kinesin family members in hepatobiliary carcinomas:from bench to bedside[J].Biomark Res,2024,12(1):30.
[8] Dekker B,Dekker J.Regulation of the mitotic chromosome folding machines [J].Biochem J,2022,479(20):2153-2173.
[9] Xue D,Cheng P,Han M,et al.An integrated bioinformatical analysis to evaluate the role of KIF4A as a prognostic biomarker for breast cancer[J].Onco Targets Ther,2018,11:4755-4768.
[10] Zhang H,Meng S,Chu K,et al.KIF4A drives gliomas growth by transcriptional repression of Rac1/Cdc42 to induce cytoskeletal remodeling in glioma cells[J].J Cancer,2022,13(15):3640-3651.
[11] Hou PF,Jiang T,Chen F,et al.KIF4A facilitates cell proliferation via induction of p21-mediated cell cycle progression and promotes metastasis in colorectal cancer[J].Cell Death Dis,2018,9(5):477.
[12] Lin N,Chen L,Zhang Y,et al.KIF4A promotes tumor progression of bladder cancer via CXCL5 dependent myeloid-derived suppressor cells recruitment[J].Sci Rep,2022,12(1):6015.
[13] Johnson N,Shapiro GI.Cyclin-dependent kinases(cdks) and the DNA damage response:rationale for cdk inhibitor-chemotherapy combinations as an anticancer strategy for solid tumors[J].Expert Opin Ther Targets,2010,14(11):1199-1212.
[14] Sun Y,Liu Y,Ma X,et al.The influence of cell cycle regulation on chemotherapy[J].Int J Mol Sci,2021,22(13):6923.
[15] Jiang ZS,Sun YZ,Wang SM,et al.Epithelial-mesenchymal transition:potential regulator of ABC transporters in tumor progression[J].J Cancer,2017,8(12):2319-2327.
[16] Kahm YJ,Kim IG,Jung U,et al.Impact of KIF4A on cancer stem cells and emt in lung cancer and glioma[J].Cancers(Basel),2023,15(23):5523.
[17] Xu Y,Xue G,Zhou L,et al.KIF4A promotes epithelial-mesenchymal transition by activating the TGF-β/SMAD signaling pathway in glioma cells[J].Mol Cell Biochem,2025,480(1):217-230.
[18] Zhang J,An L,Zhao R,et al.KIF4A promotes genomic stability and progression of endometrial cancer through regulation of TPX2 protein degradation[J].Mol Carcinog,2023,62(3):303-318.
[19] Mani N,Jiang S,Neary AE,et al.Differential regulation of single microtubules and bundles by a three-protein module[J].Nat Chem Biol,2021,17(9):964-974.
[20] Sun X,Chen P,Chen X,et al.KIF4A enhanced cell proliferation and migration via Hippo signaling and predicted a poor prognosis in esophageal squamous cell carcinoma[J].Thorac Cancer,2021,12(4):512-524.
[21] Gao H,Chen X,Cai Q,et al.Increased KIF4A expression is a potential prognostic factor in prostate cancer[J].Oncol Lett,2018,15(5):7941-7947.
[22] Zhi Y,Zhang W,Wu Z,et al.miR-223-3p targets KIF4A and promotes the oxidative stress-mediated apoptosis of breast cancer cells[J].Cancer Biother Radiopharm,2025,40(5):323-338.
[23] Li TF,Zeng HJ,Shan Z,et al.Overexpression of kinesin superfamily members as prognostic biomarkers of breast cancer[J].Cancer Cell Int,2020,20(1):123.
基本信息:
DOI：10.16846/j.issn.1004-3101.2025.06.001
中图分类号:R737.9;Q811.4
引用信息:
[1]张致涵,范宜璇,龚秀莹,等.基于生物信息学的三阴性乳腺癌关键基因筛选及生物学途径分析[J].山东第二医科大学学报,2025,47(06):401-410.DOI:10.16846/j.issn.1004-3101.2025.06.001.
基金信息:
国家自然科学基金项目(项目编号：82373043)
2025-12-15
2025-12-15