DTNBP1基因在三阴性乳腺癌中的作用及其预后价值  

Role of DTNBP1 in triple negative breast cancer and its prognostic value

作　　者：伍梦妮 徐志华[1] 陈彦[1] Wu Mengni;Xu Zhihua;Chen Yan(Department of General Surgery,First Affiliated Hospital of Soochow University,Suzhou 215006,China)

机构地区：[1]苏州大学附属第一医院普外科,215006

出　　处：《中华乳腺病杂志（电子版）》2024年第3期158-168,共11页Chinese Journal of Breast Disease(Electronic Edition)

基　　金：江苏省自然科学基金资助项目(BK20211076);江苏省研究生科研与实践创新计划项目(SJCX22_1507)。

摘　　要：目的:探讨DTNBP1基因在三阴性乳腺癌(TNBC)中的作用及预后价值。方法:收集TCGA数据库建库至今TNBC患者的RNA测序表达结果,共获得621个TNBC患者样本和32个正常样本。选取了与正常样本差异表达较大的前497个TNBC患者样本进行分析;通过生物信息学方法筛选差异表达基因;Kaplan-Meier生存分析探讨DTNBP1基因表达对497例TNBC患者预后的影响;采用主成分分析、GO及KEGG富集分析,探索DTNBP1基因的功能;用Cox单因素及多因素回归分析,寻找TNBC的预后因素,构建预后模型;采用实时定量PCR(qRT-PCR)检测DTNBP1在人正常乳腺上皮细胞(MCF-10A),激素受体阳性乳腺癌细胞(MCF-7)及TNBC(HCC1937、MDA-MB-231、MDA-MB-361、MDA-MB-468)细胞系中的表达情况;选取MDA-MB-231和MDA-MB-468细胞系进行转染实验,构建DTNBP1低表达TNBC细胞;克隆形成实验和流式细胞术分别检测DTNBP1低表达细胞和对照组细胞的增殖能力和细胞周期。结果:与正常乳腺组织相比,TNBC有3196个差异表达基因,其中2056个基因上调,1140个基因下调。以TNBC患者DTNBP1基因mRNA的中位表达量8.12为临界值,将497例TNBC患者分为DTNBP1高表达组(248例)和低表达组(249例),生存分析结果提示2组患者的中位DFS分别为9.8年和18.2年,组间比较差异有统计学意义(t=3.824,P<0.001);主成分分析结果显示,DTNBP1高、低表达2组患者共发现1138个差异表达基因,其中表达上调的基因有647个,表达下调的基因有491个。GO功能富集分析发现DTNBP1基因可能参与的生物过程有白细胞迁移、细胞外基质形成和细胞外骨架形成等;可能参与的细胞组分有含胶原的细胞外基质、细胞-基质结和焦点粘连等;可能参与的分子功能有细胞外基质结构组成、抗原结合和细胞黏附分子结合等。KEGG通路富集分析显示,DTNBP1可能参与的细胞通路有细胞周期、PI3K-Akt、MAPK、Hippo和TNF信号通路。Cox单因素分析发现年龄(HR=1.099,95%CObjective:To investigate the role and prognostic value of the DTNBP1 gene in triple negative breast cancer(TNBC).Methods:RNA sequencing expression profiles of TNBC patients were collected in the TCGA database from the establishment,yielding 621 TNBC patient samples and 32 normal samples.For accuracy,the top 497 TNBC patient samples with the most significant differential expression compared with normal samples were selected for analysis.Differentially expressed genes were screened using bioinformatics methods.The impact of DTNBP1 gene expression on the prognosis of 497 TNBC patients was assessed through Kaplan-Meier survival analysis.Principal component analysis(PCA),GO,and KEGG enrichment analyses were employed to explore the function of the DTNBP1 gene.Cox univariate and multivariate regression analyses were conducted to identify prognostic factors for TNBC and construct a prognostic model.Real-time quantitative PCR(qRT-PCR)was used to detect DTNBP1 expression in normal human mammary epithelial cells(MCF-10A),hormone receptor-positive breast cancer cells(MCF-7),and TNBC cells(HCC1937,MDA-MB-231,MDA-MB-361,MDA-MB-468).Transfection experiments were performed on MDA-MB-231 and MDA-MB-468 cells to construct DTNBP1 low-expression TNBC cells.Clonogenic assays and flow cytometry were used to assess the proliferation and cell cycle of DTNBP1 low-expression cells and control cells.Results:Compared with normal breast tissue,TNBC tissue sample exhibited 3196 differentially expressed genes,with 2056 upregulated and 1140 downregulated.Using a median DTNBP1 mRNA expression level of 8.12 as a threshold,497 TNBC patients were divided into high expression(248 cases)and low expression(249 cases)groups.Survival analysis indicated median DFS of 9.8 years for the high expression group and 18.2 years for the low expression group,with a statistically significant difference(t=3.824,P<0.001).PCA identified 1138 differentially expressed genes between high and low DTNBP1 expression groups,with 647 upregulated and 491 downregulated.GO enri

关 键 词：乳腺肿瘤 生物信息学 预后 DTNBP1 

分 类 号：R737.9[医药卫生—肿瘤]