Department of Thoracic Oncology, Cancer Center, and State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610000, P.R. China.
Mol Med Rep. 2017 Dec;16(6):8657-8664. doi: 10.3892/mmr.2017.7717. Epub 2017 Oct 4.
Gene expression data were analyzed in order to identify critical genes in breast invasive carcinoma (BRCA). Data from 1,073 BRCA samples and 99 normal samples were analyzed, which were obtained from The Cancer Genome Atlas. Differentially expressed genes (DEGs) were identified using the significance analysis of microarrays method and a functional enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery. Relevant microRNAs (miRNAs), transcription factors (TFs) and associated small molecule drugs were revealed by Fisher's exact test. Furthermore, protein‑protein interaction (PPI) information was downloaded from the Human Protein Reference Database. Interactions with a Pearson's correlation coefficient >0.5 were identified and PPI networks were subsequently constructed. A survival analysis was also conducted according to the Kaplan‑Meier method. Initially, the 1,073 BRCA samples were clustered into seven groups, and 5,394 DEGs that were identified in ≥4 groups were selected. These DEGs were involved in the cell cycle, ubiquitin‑mediated proteolysis, oxidative phosphorylation and human immunodeficiency virus infection. In addition, TFs, including Sp1 transcription factor, DAN domain BMP antagonist family member 5, MYCN proto‑oncogene, bHLH transcription factor and cAMP responsive element binding protein (CREB)1, were identified in the BRCA groups. Seven PPI networks were subsequently constructed and the top 10 hub genes were acquired, including RB transcriptional corepressor 1, inhibitor of nuclear factor (NF)‑κB kinase subunit γ, NF‑κB subunit 2, transporter 1, ATP binding cassette subfamily B member, CREB binding protein and proteasome subunit α3. A significant difference in survival was observed between the two combined groups (groups‑2, ‑4 and ‑5 vs. groups‑1, ‑3, ‑6 and ‑7). In conclusion, numerous critical genes were detected in BRCA, and relevant miRNAs, TFs and small molecule drugs were identified. These findings may advance understanding regarding the pathogenesis of BRCA.
为了鉴定乳腺浸润性癌(BRCA)中的关键基因,对基因表达数据进行了分析。对来自癌症基因组图谱的 1073 个 BRCA 样本和 99 个正常样本的数据进行了分析。使用差异表达基因(DEG)分析方法鉴定差异表达基因,并使用数据库进行功能富集分析。对Fisher 精确检验揭示的相关 microRNAs(miRNAs)、转录因子(TFs)和相关小分子药物进行了可视化和综合发现。此外,从人类蛋白质参考数据库下载蛋白质-蛋白质相互作用(PPI)信息。鉴定 Pearson 相关系数>0.5 的相互作用,并构建 PPI 网络。根据 Kaplan-Meier 方法进行生存分析。首先,将 1073 个 BRCA 样本聚类为 7 组,选择在≥4 组中鉴定到的 5394 个 DEG。这些 DEG 参与细胞周期、泛素介导的蛋白水解、氧化磷酸化和人类免疫缺陷病毒感染。此外,在 BRCA 组中鉴定到 Sp1 转录因子、DAN 结构域 BMP 拮抗剂家族成员 5、MYCN 原癌基因、bHLH 转录因子和 cAMP 反应元件结合蛋白(CREB)1 等 TFs。随后构建了 7 个 PPI 网络,并获得了前 10 个枢纽基因,包括 RB 转录核心抑制因子 1、核因子(NF)-κB 激酶亚单位 γ抑制剂、NF-κB 亚基 2、转运蛋白 1、ATP 结合盒亚家族 B 成员、CREB 结合蛋白和蛋白酶体亚基α3。两个联合组(组 2、组 4 和组 5 与组 1、组 3、组 6 和组 7)之间的生存差异显著。总之,在 BRCA 中检测到许多关键基因,并鉴定到相关的 miRNAs、TFs 和小分子药物。这些发现可能有助于深入了解 BRCA 的发病机制。