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The G protein-coupled estrogen receptor (GPER) 2 expression correlates with pro-metastatic pathways in 3 ER-negative breast cancer: a bioinformatics analysis

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  • Marianna Talia
  • Ernestina Marianna De Francesco
  • Damiano Cosimo Rigiracciolo
  • Maria Grazia Muoio
  • Lucia Muglia
  • Antonino Belfiore
  • Marcello Maggiolini
  • Andrew Sims
  • Rosamaria Lappano

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Original languageEnglish
Early online date4 Mar 2020
Publication statusE-pub ahead of print - 4 Mar 2020


The G protein-coupled estrogen receptor (GPER, formerly known as GPR30) is a seven-transmembrane receptor that mediates estrogen signals in both normal and malignant cells. In particular, GPER has been involved in the activation of diverse signaling pathways toward transcriptional and biological responses that characterize the progression of breast cancer (BC). In this context, a correlation between GPER expression and worse clinical-pathological features of BC has been suggested, although controversial data have been also reported. In order to better assess the biological significance of GPER in the aggressive estrogen receptor (ER)-negative BC, we performed a bioinformatics analysis using the information provided by The Invasive Breast Cancer Cohort of the The Cancer Genome Atlas (TCGA) project and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) datasets. Gene expression correlation and the statistical analysis were carried out with R studio base functions and the tidyverse package. Pathway enrichment analysis was evaluated with KEGG pathway on DAVID website, whereas Gene Set Enrichment Analysis (GSEA) was performed with the R package phenoTest. The survival analysis was determined with the R package survivALL. Analyzing the expression data of more than 2500 primary BC, we ascertained that GPER levels are associated with pro-migratory and metastatic genes belonging to the cell adhesion molecules (CAMs), extracellular matrix (ECM)-receptor interaction and focal adhesion (FA) signaling pathways. Thereafter, evaluating the disease free interval (DFI) in ER-negative BC patients, we found that the subjects expressing high GPER levels exhibit a shorter DFI respect to those exhibiting low GPER levels. Overall, our results may pave the way to further dissect in the breast malignancies lacking ER the network triggered by GPER, toward a better assessment of its prognostic significance and the action elicited in mediating the aggressive features of the aforementioned BC subtype.

    Research areas

  • Bioinformatics, GPER, Breast cancer, TCGA, METABRIC, cell adhesion molecules, extracellular matrix, focal adhesion

ID: 137772360