Identification of key genes involved in tamoxifen-resistant breast cancer using bioinformatics analysis

Abstract

Background 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. Methods 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. Results 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. Conclusions A number of significant hub DEGs were identified based on their degree of connectivity in the PPI network, , included MAPK1 (node degree 36), ESR1 (node degree 27), SMARCA4 (node degree 27), RANBP2 (node degree 25), and PRKCA (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.

Investigation of the Genomic and Transcriptomic Variations Underlying Tamoxifen Resistance in Breast Cancer

“…Using bioinformatic analysis Xiaopeng Wang et al discovered genes that had different expressions between tamoxifen-prone and tamoxifenresistant samples. Their results demonstrated an upregulation in NEAT1 as one of the differentially expressed genes (DEG) (105). Our ndings align with previous research and show an upregulation in the expression of NEAT1 in relation to breast cancer and tamoxifen resistance, and some of its targets include miR-548, miR-129-5p, and miR-218.…”

Dynamic proximity interaction profiling suggests that YPEL2 is involved in cellular stress surveillance

“…Although the YPEL proteins are reported to participate in cellular events, including proliferation, mitochondrial function, morphology, motility, differentiation, senescence, and death (Aerts et al, 2006b ; Baek et al, 2021 ; Baker, 2003 ; Blanco‐Sanchez et al, 2020 ; Dean et al, 2022 ; Farlie et al, 2001 ; Garcıá et al, 2019 ; Hosono et al, 2010 ; Jun et al, 2007 ; K. D. Kelley et al, 2010 ; J. H. Kim et al, 2020 ; Kong et al, 2018 ; J. Y. Lee et al, 2017 ; W. Li et al, 2022 ; Liang et al, 2010 ; Mattebo et al, 2021 ; Oki et al, 2016 ; Tan et al, 2015 ; Tuttle et al, 2012 ; J. Zhang et al, 2016 ) studies on YPEL2 are limited. Deregulated expression of YPEL2 is reported in various pathologies, including ccRCC (L. Wang et al, 2022 ), breast cancer (K. D. Kelley et al, 2010 ; Mascia et al, 2022 ; X. Wang & Wang, 2021 ), chronic idiopathic urticaria, and active hives (Lin et al, 2017 ). Using publically available pan‐cancer databases, for example, it was reported that YPEL2 , along with YPEL1 and YPEL5 , is differentially expressed in ccRCC and that increased expressions of YPEL1 , YPEL2 , and YPEL5 were associated with improved overall as well as disease‐specific survival of ccRCC patients (L. Wang et al, 2022 ).…”

Favipiravir, an antiviral drug, in combination with tamoxifen exerts synergistic effect in tamoxifen-resistant breast cancer cells via hTERT inhibition

“…TAM is one of the most chemotherapeutic medications used to treat breast cancer, however with time, cancer cells become resistant to TAM 8 – 11 . Some genes have been found to be associated with mechanisms of tamoxifen resistance 39 . Thus, exploration of more effective strategies is demanded to overcome resistance in breast cancer cells, improve TAM efficacy, and decrease undesirable side effects 9 , 38 – 40 .…”