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Syndecan-1 as an immunogene in Triple-negative breast cancer: regulation tumor-infiltrating lymphocyte in the tumor microenviroment and EMT by TGFb1/Smad pathway

BACKGROUND: Immune checkpoint inhibitors are the most studied forms of immunotherapy for triple-negative breast cancer (TNBC). The Cancer Genome Map (TCGA) and METABRIC project provide large-scale cancer samples that can be used for comprehensive and reliable immunity-related gene research. METHODS:...

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Autores principales: Zhong, Ying, Li, Fangyuan, Zhang, Sumei, Yang, Zhenli, Ren, Xinyu, Cao, Xi, Xu, Yali, Guo, Dan, Zhou, Yidong, Mao, Feng, Shen, Songjie, Sun, Qiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10111802/
https://www.ncbi.nlm.nih.gov/pubmed/37069585
http://dx.doi.org/10.1186/s12935-023-02917-7
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author Zhong, Ying
Li, Fangyuan
Zhang, Sumei
Yang, Zhenli
Ren, Xinyu
Cao, Xi
Xu, Yali
Guo, Dan
Zhou, Yidong
Mao, Feng
Shen, Songjie
Sun, Qiang
author_facet Zhong, Ying
Li, Fangyuan
Zhang, Sumei
Yang, Zhenli
Ren, Xinyu
Cao, Xi
Xu, Yali
Guo, Dan
Zhou, Yidong
Mao, Feng
Shen, Songjie
Sun, Qiang
author_sort Zhong, Ying
collection PubMed
description BACKGROUND: Immune checkpoint inhibitors are the most studied forms of immunotherapy for triple-negative breast cancer (TNBC). The Cancer Genome Map (TCGA) and METABRIC project provide large-scale cancer samples that can be used for comprehensive and reliable immunity-related gene research. METHODS: We analyzed data from TCGA and METABRIC and established an immunity-related gene prognosis model for breast cancer. The SDC1 expression in tumor and cancer associated fibroblasts (CAFs) was then observed in 282 TNBC patients by immunohistochemistry. The effects of SDC1 on MDA-MB-231 proliferation, migration and invasion were evaluated. Qualitative real-time PCR and western blotting were performed to identify mRNA and protein expression, respectively. RESULTS: SDC1, as a key immunity-related gene, was significantly correlated with survival in the TCGA and METABRIC databases, while SDC1 was found to be highly expressed in TNBC in the METABRIC database. In the TNBC cohort, patients with high SDC1 expression in tumor cells and low expression in CAFs had significantly lower disease-free survival (DFS) and fewer tumor-infiltrating lymphocytes (TILs). The downregulation of SDC1 decreased the proliferation of MDA-MB-231, while promoting the migration of MDA-MB-231 cells by reducing the gene expression of E-cadherin and TGFb1 and activating p-Smad2 and p-Smad3 expression. CONCLUSION: SDC1 is a key immunity-related gene that is highly expressed TNBC patients. Patients with high SDC1 expression in tumors and low expression in CAFs had poor prognoses and low TILs. Our findings also suggest that SDC1 regulates the migration of MDA-MB-231 breast cancer cells through a TGFb1-Smad and E-cadherin-dependent mechanism. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-023-02917-7.
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spelling pubmed-101118022023-04-19 Syndecan-1 as an immunogene in Triple-negative breast cancer: regulation tumor-infiltrating lymphocyte in the tumor microenviroment and EMT by TGFb1/Smad pathway Zhong, Ying Li, Fangyuan Zhang, Sumei Yang, Zhenli Ren, Xinyu Cao, Xi Xu, Yali Guo, Dan Zhou, Yidong Mao, Feng Shen, Songjie Sun, Qiang Cancer Cell Int Research BACKGROUND: Immune checkpoint inhibitors are the most studied forms of immunotherapy for triple-negative breast cancer (TNBC). The Cancer Genome Map (TCGA) and METABRIC project provide large-scale cancer samples that can be used for comprehensive and reliable immunity-related gene research. METHODS: We analyzed data from TCGA and METABRIC and established an immunity-related gene prognosis model for breast cancer. The SDC1 expression in tumor and cancer associated fibroblasts (CAFs) was then observed in 282 TNBC patients by immunohistochemistry. The effects of SDC1 on MDA-MB-231 proliferation, migration and invasion were evaluated. Qualitative real-time PCR and western blotting were performed to identify mRNA and protein expression, respectively. RESULTS: SDC1, as a key immunity-related gene, was significantly correlated with survival in the TCGA and METABRIC databases, while SDC1 was found to be highly expressed in TNBC in the METABRIC database. In the TNBC cohort, patients with high SDC1 expression in tumor cells and low expression in CAFs had significantly lower disease-free survival (DFS) and fewer tumor-infiltrating lymphocytes (TILs). The downregulation of SDC1 decreased the proliferation of MDA-MB-231, while promoting the migration of MDA-MB-231 cells by reducing the gene expression of E-cadherin and TGFb1 and activating p-Smad2 and p-Smad3 expression. CONCLUSION: SDC1 is a key immunity-related gene that is highly expressed TNBC patients. Patients with high SDC1 expression in tumors and low expression in CAFs had poor prognoses and low TILs. Our findings also suggest that SDC1 regulates the migration of MDA-MB-231 breast cancer cells through a TGFb1-Smad and E-cadherin-dependent mechanism. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-023-02917-7. BioMed Central 2023-04-17 /pmc/articles/PMC10111802/ /pubmed/37069585 http://dx.doi.org/10.1186/s12935-023-02917-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Zhong, Ying
Li, Fangyuan
Zhang, Sumei
Yang, Zhenli
Ren, Xinyu
Cao, Xi
Xu, Yali
Guo, Dan
Zhou, Yidong
Mao, Feng
Shen, Songjie
Sun, Qiang
Syndecan-1 as an immunogene in Triple-negative breast cancer: regulation tumor-infiltrating lymphocyte in the tumor microenviroment and EMT by TGFb1/Smad pathway
title Syndecan-1 as an immunogene in Triple-negative breast cancer: regulation tumor-infiltrating lymphocyte in the tumor microenviroment and EMT by TGFb1/Smad pathway
title_full Syndecan-1 as an immunogene in Triple-negative breast cancer: regulation tumor-infiltrating lymphocyte in the tumor microenviroment and EMT by TGFb1/Smad pathway
title_fullStr Syndecan-1 as an immunogene in Triple-negative breast cancer: regulation tumor-infiltrating lymphocyte in the tumor microenviroment and EMT by TGFb1/Smad pathway
title_full_unstemmed Syndecan-1 as an immunogene in Triple-negative breast cancer: regulation tumor-infiltrating lymphocyte in the tumor microenviroment and EMT by TGFb1/Smad pathway
title_short Syndecan-1 as an immunogene in Triple-negative breast cancer: regulation tumor-infiltrating lymphocyte in the tumor microenviroment and EMT by TGFb1/Smad pathway
title_sort syndecan-1 as an immunogene in triple-negative breast cancer: regulation tumor-infiltrating lymphocyte in the tumor microenviroment and emt by tgfb1/smad pathway
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10111802/
https://www.ncbi.nlm.nih.gov/pubmed/37069585
http://dx.doi.org/10.1186/s12935-023-02917-7
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