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High GPER expression in triple-negative breast cancer is linked to pro-metastatic pathways and predicts poor patient outcomes

Triple-negative breast cancer (TNBC) is a particularly aggressive and heterogeneous disease with few effective targeted therapies and precision therapeutic options over a long period. It is generally considered that TNBC is an estrogen-independent breast cancer, while a new estrogen receptor, namely...

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Autores principales: Xu, Ting, Ma, Ding, Chen, Sheng, Tang, Rui, Yang, Jianling, Meng, Chunhui, Feng, Yang, Liu, Li, Wang, Jiangfen, Luo, Haojun, Yu, Keda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9427744/
https://www.ncbi.nlm.nih.gov/pubmed/36042244
http://dx.doi.org/10.1038/s41523-022-00472-4
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author Xu, Ting
Ma, Ding
Chen, Sheng
Tang, Rui
Yang, Jianling
Meng, Chunhui
Feng, Yang
Liu, Li
Wang, Jiangfen
Luo, Haojun
Yu, Keda
author_facet Xu, Ting
Ma, Ding
Chen, Sheng
Tang, Rui
Yang, Jianling
Meng, Chunhui
Feng, Yang
Liu, Li
Wang, Jiangfen
Luo, Haojun
Yu, Keda
author_sort Xu, Ting
collection PubMed
description Triple-negative breast cancer (TNBC) is a particularly aggressive and heterogeneous disease with few effective targeted therapies and precision therapeutic options over a long period. It is generally considered that TNBC is an estrogen-independent breast cancer, while a new estrogen receptor, namely G protein-coupled estrogen receptor (GPER), is demonstrated to mediate estrogenic actions in TNBC. Based on our transcriptomic analysis, expression of GPER was correlated with clinicopathological variables and survival of 360 TNBC patients. GPER expression at mRNA level was significantly correlated with immunohistochemistry scoring in 12 randomly chosen samples. According to the cutoff value, 26.4% (95/360) of patients showed high GPER expression and significant correlation with the mRNA subtype of TNBC (P = 0.001), total metastatic events (P = 0.019) and liver metastasis (P = 0.011). In quantitative comparison, GPER abundance is correlated with the high-risk subtype of TNBC. At a median follow-up interval of 67.1 months, a significant trend towards reduced distant metastasis-free survival (DMFS) (P = 0.014) was found by Kaplan–Meier analysis in patients with high GPER expression. Furthermore, univariate analysis confirmed that GPER was a significant prognostic factor for DMFS in TNBC patients. Besides, high GPER expression was significantly linked to the worse survival in patients with lymph node metastasis, TNM stage III as well as nuclear grade G3 tumors. Transcriptome-based bioinformatics analysis revealed that GPER was linked to pro-metastatic pathways in our cohort. These results may supply new insights into GPER-mediated estrogen carcinogenesis in TNBC, thus providing a potential strategy for endocrine therapy of TNBC.
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spelling pubmed-94277442022-09-01 High GPER expression in triple-negative breast cancer is linked to pro-metastatic pathways and predicts poor patient outcomes Xu, Ting Ma, Ding Chen, Sheng Tang, Rui Yang, Jianling Meng, Chunhui Feng, Yang Liu, Li Wang, Jiangfen Luo, Haojun Yu, Keda NPJ Breast Cancer Article Triple-negative breast cancer (TNBC) is a particularly aggressive and heterogeneous disease with few effective targeted therapies and precision therapeutic options over a long period. It is generally considered that TNBC is an estrogen-independent breast cancer, while a new estrogen receptor, namely G protein-coupled estrogen receptor (GPER), is demonstrated to mediate estrogenic actions in TNBC. Based on our transcriptomic analysis, expression of GPER was correlated with clinicopathological variables and survival of 360 TNBC patients. GPER expression at mRNA level was significantly correlated with immunohistochemistry scoring in 12 randomly chosen samples. According to the cutoff value, 26.4% (95/360) of patients showed high GPER expression and significant correlation with the mRNA subtype of TNBC (P = 0.001), total metastatic events (P = 0.019) and liver metastasis (P = 0.011). In quantitative comparison, GPER abundance is correlated with the high-risk subtype of TNBC. At a median follow-up interval of 67.1 months, a significant trend towards reduced distant metastasis-free survival (DMFS) (P = 0.014) was found by Kaplan–Meier analysis in patients with high GPER expression. Furthermore, univariate analysis confirmed that GPER was a significant prognostic factor for DMFS in TNBC patients. Besides, high GPER expression was significantly linked to the worse survival in patients with lymph node metastasis, TNM stage III as well as nuclear grade G3 tumors. Transcriptome-based bioinformatics analysis revealed that GPER was linked to pro-metastatic pathways in our cohort. These results may supply new insights into GPER-mediated estrogen carcinogenesis in TNBC, thus providing a potential strategy for endocrine therapy of TNBC. Nature Publishing Group UK 2022-08-30 /pmc/articles/PMC9427744/ /pubmed/36042244 http://dx.doi.org/10.1038/s41523-022-00472-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Xu, Ting
Ma, Ding
Chen, Sheng
Tang, Rui
Yang, Jianling
Meng, Chunhui
Feng, Yang
Liu, Li
Wang, Jiangfen
Luo, Haojun
Yu, Keda
High GPER expression in triple-negative breast cancer is linked to pro-metastatic pathways and predicts poor patient outcomes
title High GPER expression in triple-negative breast cancer is linked to pro-metastatic pathways and predicts poor patient outcomes
title_full High GPER expression in triple-negative breast cancer is linked to pro-metastatic pathways and predicts poor patient outcomes
title_fullStr High GPER expression in triple-negative breast cancer is linked to pro-metastatic pathways and predicts poor patient outcomes
title_full_unstemmed High GPER expression in triple-negative breast cancer is linked to pro-metastatic pathways and predicts poor patient outcomes
title_short High GPER expression in triple-negative breast cancer is linked to pro-metastatic pathways and predicts poor patient outcomes
title_sort high gper expression in triple-negative breast cancer is linked to pro-metastatic pathways and predicts poor patient outcomes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9427744/
https://www.ncbi.nlm.nih.gov/pubmed/36042244
http://dx.doi.org/10.1038/s41523-022-00472-4
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