Wang Xiaopeng, Wang Shixia
Department of Outpatient and Emergency, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Transl Cancer Res. 2021 Dec;10(12):5246-5257. doi: 10.21037/tcr-21-1276.
The purpose of the present study was to investigate the molecular mechanisms of tamoxifen resistance in breast cancer and to identify potential targets for antitamoxifen resistance.
Differentially expressed genes (DEGs) in tamoxifen-resistant and tamoxifen-sensitive breast cancer cells were assessed using the GSE67916 dataset acquired from the Gene Expression Omnibus database. Gene ontology (GO) and pathway enrichment analyses were applied to investigate the functions and pathways of the DEGs. Subsequently, the protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING), and subnetworks were further analyzed by Molecular Complex Detection (MCODE). The PPI network and subnetworks were visualized using Cytoscape software.
In total, 438 DEGs were identified, of which 300 were upregulated and 138 were downregulated. The DEGs were significantly enriched in the protein binding, cellular response to estradiol stimulus, and immune response GO terms while the most significant pathways included the mitogen-activated protein kinase (MAPK) signaling pathway in cancer. The PPI network of DEGs was constructed with 288 nodes and 629 edges, and 2 subnetworks were screened out from the entire network.
A number of significant hub DEGs were identified based on their degree of connectivity in the PPI network, , included (node degree 36), (node degree 27), (node degree 27), (node degree 25), and (node degree 21). These critical hub genes were found to be related to tamoxifen resistance in breast cancer. The results of this study further the understanding of tamoxifen resistance at the molecular level and identify potential therapeutic targets for tamoxifen-resistant breast cancer.
本研究旨在探讨乳腺癌中他莫昔芬耐药的分子机制，并确定抗他莫昔芬耐药的潜在靶点。
使用从基因表达综合数据库获取的GSE67916数据集评估他莫昔芬耐药和他莫昔芬敏感的乳腺癌细胞中的差异表达基因（DEG）。应用基因本体（GO）和通路富集分析来研究DEG的功能和通路。随后，使用搜索相互作用基因的工具（STRING）构建蛋白质-蛋白质相互作用（PPI）网络，并通过分子复合物检测（MCODE）进一步分析子网。使用Cytoscape软件可视化PPI网络和子网。
总共鉴定出438个DEG，其中300个上调，138个下调。这些DEG在蛋白质结合、细胞对雌二醇刺激的反应和免疫反应GO术语中显著富集，而最显著的通路包括癌症中的丝裂原活化蛋白激酶（MAPK）信号通路。构建了包含288个节点和629条边的DEG的PPI网络，并从整个网络中筛选出2个子网。
基于它们在PPI网络中的连接程度鉴定出了许多重要的枢纽DEG，包括（节点度36）、（节点度27）、（节点度27）、（节点度25）和（节点度21）。发现这些关键的枢纽基因与乳腺癌中的他莫昔芬耐药有关。本研究结果进一步加深了对他莫昔芬耐药的分子水平的理解，并确定了他莫昔芬耐药乳腺癌的潜在治疗靶点。
