Qi Feng, Qin Wen-Xing, Zang Yuan-Sheng
Department of Oncology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
Oncol Lett. 2019 Mar;17(3):2905-2914. doi: 10.3892/ol.2019.9884. Epub 2019 Jan 3.
BRAC1 has multiple important interactions with triple-negative breast cancer, the specific molecular characteristics of this interaction, however, have not yet been completely elucidated. By examining cell signaling pathways, important information for comprehending the potential mechanisms of this cancer may become known. The aim of the present study was to identify the effects of BRAC1 and to find the signaling pathway(s) involved in the pathogenic mechanism of triple-negative breast cancer. In this study, GSE27447 microarray data were obtained from the Gene Expression Omnibus (GEO) database of the National Center for Biotechnology Information, and differentially expressed genes (DEGs) from GSE27447 were distinguished by Significant Analysis of Microarray. Gene ontology (GO) analysis was carried out on 132 upregulated and 198 downregulated genes with DAVID. The signaling was forecast by the Kyoto Encyclopedia of Genes and Genomes (KEGG). Transcription factors were recognized by TFatS. The BRAC1 relevant protein-protein interaction networks (PPI) were fixed by STRING and visualized by CytoScape. Overall, the upregulated DEGs, which included CR2, IGHM, PRKCB, CARD11, PLCG2, CD79A, IGKC and CD27, were primarily enriched in the terms associated with immune responses, and the downregulated DEGs, which included STARD3, ALDH8A1, SRD5A3, CACNA1H, UGT2B4, SDR16C5 and MED1, were primarily enriched in the hormone metabolic process. In addition, 13 pathways, such as the B-cell receptor-signaling pathway, the hormone synthesis signaling pathway and the oxytocin-signaling pathway, were chosen. MYC, SP1 and CTNNB1 were determined to be enriched in triple-negative breast cancer. A total of 8 genes were identified to be downregulated in the BRAC1-related PPI network. The results of the present study show a fresh angle on the molecular mechanism of triple-negative breast cancer and indicate a possible target for its treatment.
BRAC1与三阴性乳腺癌存在多种重要相互作用，然而，这种相互作用的具体分子特征尚未完全阐明。通过研究细胞信号通路，或许能够了解这种癌症潜在机制的重要信息。本研究的目的是确定BRAC1的作用，并找出参与三阴性乳腺癌致病机制的信号通路。在本研究中，从美国国立生物技术信息中心的基因表达综合数据库（GEO）中获取了GSE27447芯片数据，并通过微阵列显著性分析鉴别出GSE27447中的差异表达基因（DEG）。使用DAVID对132个上调基因和198个下调基因进行基因本体（GO）分析。通过京都基因与基因组百科全书（KEGG）预测信号通路。利用TFatS识别转录因子。通过STRING确定BRAC1相关的蛋白质-蛋白质相互作用网络（PPI），并使用CytoScape进行可视化。总体而言，上调的DEG，包括CR2、IGHM、PRKCB、CARD11、PLCG2、CD79A、IGKC和CD27，主要富集在与免疫反应相关的术语中，而下调的DEG，包括STARD3、ALDH8A1、SRD5A3、CACNA1H、UGT2B4、SDR16C5和MED1，主要富集在激素代谢过程中。此外，还选择了13条信号通路，如B细胞受体信号通路、激素合成信号通路和催产素信号通路。确定MYC、SP1和CTNNB1在三阴性乳腺癌中富集。在BRAC1相关的PPI网络中总共鉴定出8个下调基因。本研究结果为三阴性乳腺癌的分子机制提供了新视角，并指出了其治疗的可能靶点。
