Page 41 - 南京医科大学学报自然科学版

第41卷第12期 南京医科大学学报（自然科学版）
2021年12月 Journal of Nanjing Medical University（Natural Sciences） ·1747 ·

·基础医学·

应用生物信息学分析正常女性不同乳腺密度差异表达基因

徐文秀，蒋梦萍，王丹丹，张 建，吴 旸，张 薇，唐金海 *
南京医科大学第一附属医院普外科，江苏 南京 210029

［摘 要］ 目的：应用生物信息学技术筛选高乳腺密度和低乳腺密度的正常女性的差异基因并分析其富集通路，为致密型乳
腺女性乳腺癌早期诊断、靶向治疗和预后评估提供理论依据。方法：从GEO数据库获取GSE38506数据集，使用GEO2R筛选
差异表达基因。使用DAVID数据库进行GO、KEGG富集分析，并应用STRING及Cytoscape软件的 CytoHubba插件进行蛋白相
互作用网络分析，筛选出Hub基因。最后使用bcGenExMiner在线工具对这5个Hub基因进行预后分析。结果：从GSE38506基
因芯片共筛选出830个显著差异表达基因，其中上调基因442个，下调基因388个。富集分析显示，差异表达基因主要涉及信
号转导、GTP酶活性的正调控、固有免疫反应、细胞黏附、细胞质膜、细胞表面、细胞连接、ATP结合、肌动蛋白结合、转录因子结
合等。共筛选出2个核心模块和5个Hub基因，包括EGFR、JUN、CDC42、SRC、RAC1，并且它们都与乳腺癌预后相关。结论：通
过生物信息学筛选出了正常女性乳腺密度相关的 5个核心基因，可能对乳腺癌的发生发展和预后存在一定影响，是潜在的致
密型乳腺女性易患乳腺癌的分子学标志物和靶向治疗新位点。
［关键词］ 乳房钼靶密度；差异表达基因；富集分析；蛋白质互相作用网络；Hub基因
［中图分类号］ R737.9 ［文献标志码］ A ［文章编号］ 1007⁃4368（2021）12⁃1747⁃07
doi：10.7655/NYDXBNS20211206

Exploring the key genes and pathways in healthy women with different mammographic
density using bioinformatics analysis

XU Wenxiu，JIANG Mengping，WANG Dandan，ZHANG Jian，WU Yang，ZHANG Wei，TANG Jinhai *
Department of General Surgery，the First Affiliated Hospital of Nanjing Medical University，Nanjing 210029，China

［Abstract］ Objective：Bioinformatics analysis was applied to explore the differentially expressed genes（DEG）in normal women with
high breast density and low breast density and analyze their enrichment pathways，so as to provide theoretical basis for early diagnosis，
targeted therapy and prognosis assessment of breast cancer patients with dense breast. Methods：GSE38506 data set was obtained from
the GEO database and DEGs were screened using GEO2R. Enrichment analysis of GO and KEGG was performed using DAVID
database. CytoHubba plug ⁃ in of STRING and Cytoscape software was used for protein interaction network analysis and Hub gene
screening. Finally，the online tool bcGenExMiner was used to analyze the prognosis of these 5 Hub genes. Results：A total of 830
significantly DEGs were screened from GSE38506 gene chip，among which 442 genes were up⁃regulated and 388 genes were down⁃
regulated. Enrichment analysis showed that DEGs were mainly involved in signal transduction，positive regulation of GTPase activity，
innate immune response，cell adhesion，cytoplasmic membrane，cell surface，cell connection，ATP binding，actin binding，transcription
factor binding，and so on. A total of 2 core modules and 5 Hub genes were screened，including EGFR，JUN proto⁃Oncogene，CDC42，
SRC proto⁃oncogene，RAC1，and they were all associated with breast cancer prognosis. Conclusion：In this study，5 Hub genes related
to mammographic density in healthy women were screened through bioinformatics，which may have certain influence on the occurrence，
development and prognosis of breast cancer，and are potential molecular markers and new targeted therapy sites for breast cancer
patients with dense breast.
［Key words］ mammographic density；differentially expressed genes；enrichment analysis；protein⁃protein interaction network；Hub
genes
［J Nanjing Med Univ，2021，41（12）：1747⁃1752，1773］

［基金项目］ 国家重点研发计划（2016YFC0905900）；国家自然科学基金（81872365）；江苏省社会发展“临床前沿技术”重点项
目（BE2019731）
∗
通信作者（Corresponding author），E⁃mail：jhtang@njmu.edu.cn