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Multiplexed immunofluorescence analysis of CAF-markers, EZH2 and FOXM1 in gastric tissue: associations with clinicopathological parameters and clinical outcomes
BACKGROUND: The aim of this study is to explore the expression and clinical relevance of CAF-associated markers, EZH2 and FOXM1 in gastric samples. METHODS: Protein expression were detected and evaluated by multi-plex immunofluorescence (mIF) in 93 cases of gastric cancer (GC) and 31 cases of gastri...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9675203/ https://www.ncbi.nlm.nih.gov/pubmed/36401232 http://dx.doi.org/10.1186/s12885-022-10312-0 |
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author | Sun, Hui Wang, Xin Zhang, Xiaoyan Wang, Xu Tan, Cong Weng, Weiwei Zhang, Meng Ni, Shujuan Wang, Lei Huang, Dan Xu, Midie Sheng, Weiqi |
author_facet | Sun, Hui Wang, Xin Zhang, Xiaoyan Wang, Xu Tan, Cong Weng, Weiwei Zhang, Meng Ni, Shujuan Wang, Lei Huang, Dan Xu, Midie Sheng, Weiqi |
author_sort | Sun, Hui |
collection | PubMed |
description | BACKGROUND: The aim of this study is to explore the expression and clinical relevance of CAF-associated markers, EZH2 and FOXM1 in gastric samples. METHODS: Protein expression were detected and evaluated by multi-plex immunofluorescence (mIF) in 93 cases of gastric cancer (GC) and 31 cases of gastric intraepithelial neoplasia (GIN). The correlation among their expression, and the relationship of them with clinicopathological parameters and prognosis in GC were then analyzed. RESULTS: FAP was specific expressed in the CAFs of GC samples, and thus be utilized as a CAF-associated marker in our subsequently analysis. The immunostaining of EZH2, FOXM1 and FAP were significantly upregulated in patients with GC tissues than in those normal gastric mucosa or GIN tissues. The average fluorescence intensity of FAP was slightly positively correlated with EZH2 in GC, GIN and normal samples, whereas the percentage of FAP positive cells has no correlation with that of EZH2. Both the percentage of positive cells and the average fluorescence intensity of FOXM1 were positively correlated with that of FAP and EZH2 in GC, GIN and normal samples, except for FOXM1 and EZH2 expression in normal tissue samples. No significant association was observed between FAP expression and any clinicopathological parameters, whereas the positive frequency of EZH2 and FOXM1 were correlated with tumor location significantly and tumor invasion depth, respectively. In addition, there was strong positive correlations between FAP protein expression and overall survival (OS) and disease-free survival (DFS), and EZH2 expression was positively associated with OS in patients with GC. Furthermore, EZH2 and FAP protein expression was an independent prognostic factor for OS and DFS, respectively. CONCLUSIONS: These results suggest that both EZH2 and FOXM1 expression was positively associated with CAFs abundance in GC. They may be potential cellular target for therapeutic intervention, especially in patients with a large number of CAFs. |
format | Online Article Text |
id | pubmed-9675203 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-96752032022-11-20 Multiplexed immunofluorescence analysis of CAF-markers, EZH2 and FOXM1 in gastric tissue: associations with clinicopathological parameters and clinical outcomes Sun, Hui Wang, Xin Zhang, Xiaoyan Wang, Xu Tan, Cong Weng, Weiwei Zhang, Meng Ni, Shujuan Wang, Lei Huang, Dan Xu, Midie Sheng, Weiqi BMC Cancer Research BACKGROUND: The aim of this study is to explore the expression and clinical relevance of CAF-associated markers, EZH2 and FOXM1 in gastric samples. METHODS: Protein expression were detected and evaluated by multi-plex immunofluorescence (mIF) in 93 cases of gastric cancer (GC) and 31 cases of gastric intraepithelial neoplasia (GIN). The correlation among their expression, and the relationship of them with clinicopathological parameters and prognosis in GC were then analyzed. RESULTS: FAP was specific expressed in the CAFs of GC samples, and thus be utilized as a CAF-associated marker in our subsequently analysis. The immunostaining of EZH2, FOXM1 and FAP were significantly upregulated in patients with GC tissues than in those normal gastric mucosa or GIN tissues. The average fluorescence intensity of FAP was slightly positively correlated with EZH2 in GC, GIN and normal samples, whereas the percentage of FAP positive cells has no correlation with that of EZH2. Both the percentage of positive cells and the average fluorescence intensity of FOXM1 were positively correlated with that of FAP and EZH2 in GC, GIN and normal samples, except for FOXM1 and EZH2 expression in normal tissue samples. No significant association was observed between FAP expression and any clinicopathological parameters, whereas the positive frequency of EZH2 and FOXM1 were correlated with tumor location significantly and tumor invasion depth, respectively. In addition, there was strong positive correlations between FAP protein expression and overall survival (OS) and disease-free survival (DFS), and EZH2 expression was positively associated with OS in patients with GC. Furthermore, EZH2 and FAP protein expression was an independent prognostic factor for OS and DFS, respectively. CONCLUSIONS: These results suggest that both EZH2 and FOXM1 expression was positively associated with CAFs abundance in GC. They may be potential cellular target for therapeutic intervention, especially in patients with a large number of CAFs. BioMed Central 2022-11-18 /pmc/articles/PMC9675203/ /pubmed/36401232 http://dx.doi.org/10.1186/s12885-022-10312-0 Text en © The Author(s) 2022 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 Sun, Hui Wang, Xin Zhang, Xiaoyan Wang, Xu Tan, Cong Weng, Weiwei Zhang, Meng Ni, Shujuan Wang, Lei Huang, Dan Xu, Midie Sheng, Weiqi Multiplexed immunofluorescence analysis of CAF-markers, EZH2 and FOXM1 in gastric tissue: associations with clinicopathological parameters and clinical outcomes |
title | Multiplexed immunofluorescence analysis of CAF-markers, EZH2 and FOXM1 in gastric tissue: associations with clinicopathological parameters and clinical outcomes |
title_full | Multiplexed immunofluorescence analysis of CAF-markers, EZH2 and FOXM1 in gastric tissue: associations with clinicopathological parameters and clinical outcomes |
title_fullStr | Multiplexed immunofluorescence analysis of CAF-markers, EZH2 and FOXM1 in gastric tissue: associations with clinicopathological parameters and clinical outcomes |
title_full_unstemmed | Multiplexed immunofluorescence analysis of CAF-markers, EZH2 and FOXM1 in gastric tissue: associations with clinicopathological parameters and clinical outcomes |
title_short | Multiplexed immunofluorescence analysis of CAF-markers, EZH2 and FOXM1 in gastric tissue: associations with clinicopathological parameters and clinical outcomes |
title_sort | multiplexed immunofluorescence analysis of caf-markers, ezh2 and foxm1 in gastric tissue: associations with clinicopathological parameters and clinical outcomes |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9675203/ https://www.ncbi.nlm.nih.gov/pubmed/36401232 http://dx.doi.org/10.1186/s12885-022-10312-0 |
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