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Missense mutations of GPER1 in breast invasive carcinoma: Exploring gene expression, signal transduction and immune cell infiltration with insights from cellular pharmacology

  • Authors:
    • Yu Zhang
    • Chong Du
    • Shu-Qun Zhang
    • Hui-Xia Yu
    • Hao-Lin Mo
    • Qi-Yuan Yang
    • Yang Li
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, P.R. China, Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 22
    |
    Published online on: November 29, 2024
       https://doi.org/10.3892/br.2024.1900
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Abstract

G protein‑coupled estrogen receptor 1 (GPER1) plays a crucial role in the progression of breast cancer and has emerged as a promising therapeutic target. However, while missense mutations in GPER1 have been detected in breast invasive carcinoma (BIC) samples, the resulting molecular, cellular and pharmacological changes remain unclear. The present study categorized BIC samples from The Cancer Genome Atlas database based on mutation information available in the cBioPortal database. Subsequently, survival analysis was conducted and the samples screened for differentially expressed genes (DEGs). Using these DEGs, the present study performed Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, protein‑protein interaction network analysis and hub gene selection. After assessing the prognostic value of hub genes, the immune cell infiltration between mutant and wild‑type (WT) groups was analyzed. Finally, a luciferase reporter system was used to assess the cyclic AMP (cAMP) production mediated by GPER1 following treatment with the agonist G‑1 for each mutation. The results revealed a significant decrease in progression‑free survival and disease‑specific survival in the GPER1 mutant group compared with the WT group. Gene expression analysis identified 60 DEGs, all of which were upregulated and significantly enriched in GO terms related to tumor progression, such as organic anion transport, glycosaminoglycan binding and monoatomic ion‑gated channel activity. DEGs were also significantly enriched in the PI3K‑Akt signaling pathway in KEGG. Hub gene selection and prognostic evaluation identified three genes significantly associated with survival: IL33, STAB2 and CFTR. Immune cell infiltration analysis revealed a significant decrease in CD8 T cell content in the GPER1 mutant group compared with the WT group. Luciferase reporter assays demonstrated that four missense mutations in GPER1 (L129M, E218Q, S235F and A345G) significantly attenuated the induction of cyclic adenosine monophosphate production mediated by its agonist. These findings provided valuable insights for the design of breast cancer drugs targeting GPER1 and for precision medicine initiatives.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang Y, Du C, Zhang S, Yu H, Mo H, Yang Q and Li Y: Missense mutations of GPER1 in breast invasive carcinoma: Exploring gene expression, signal transduction and immune cell infiltration with insights from cellular pharmacology. Biomed Rep 22: 22, 2025.
APA
Zhang, Y., Du, C., Zhang, S., Yu, H., Mo, H., Yang, Q., & Li, Y. (2025). Missense mutations of GPER1 in breast invasive carcinoma: Exploring gene expression, signal transduction and immune cell infiltration with insights from cellular pharmacology. Biomedical Reports, 22, 22. https://doi.org/10.3892/br.2024.1900
MLA
Zhang, Y., Du, C., Zhang, S., Yu, H., Mo, H., Yang, Q., Li, Y."Missense mutations of GPER1 in breast invasive carcinoma: Exploring gene expression, signal transduction and immune cell infiltration with insights from cellular pharmacology". Biomedical Reports 22.2 (2025): 22.
Chicago
Zhang, Y., Du, C., Zhang, S., Yu, H., Mo, H., Yang, Q., Li, Y."Missense mutations of GPER1 in breast invasive carcinoma: Exploring gene expression, signal transduction and immune cell infiltration with insights from cellular pharmacology". Biomedical Reports 22, no. 2 (2025): 22. https://doi.org/10.3892/br.2024.1900
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang Y, Du C, Zhang S, Yu H, Mo H, Yang Q and Li Y: Missense mutations of GPER1 in breast invasive carcinoma: Exploring gene expression, signal transduction and immune cell infiltration with insights from cellular pharmacology. Biomed Rep 22: 22, 2025.
APA
Zhang, Y., Du, C., Zhang, S., Yu, H., Mo, H., Yang, Q., & Li, Y. (2025). Missense mutations of GPER1 in breast invasive carcinoma: Exploring gene expression, signal transduction and immune cell infiltration with insights from cellular pharmacology. Biomedical Reports, 22, 22. https://doi.org/10.3892/br.2024.1900
MLA
Zhang, Y., Du, C., Zhang, S., Yu, H., Mo, H., Yang, Q., Li, Y."Missense mutations of GPER1 in breast invasive carcinoma: Exploring gene expression, signal transduction and immune cell infiltration with insights from cellular pharmacology". Biomedical Reports 22.2 (2025): 22.
Chicago
Zhang, Y., Du, C., Zhang, S., Yu, H., Mo, H., Yang, Q., Li, Y."Missense mutations of GPER1 in breast invasive carcinoma: Exploring gene expression, signal transduction and immune cell infiltration with insights from cellular pharmacology". Biomedical Reports 22, no. 2 (2025): 22. https://doi.org/10.3892/br.2024.1900
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