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GMFG Has Potential to Be a Novel Prognostic Marker and Related to Immune Infiltrates in Breast Cancer

A growing amount of evidence has indicated immune genes perform a crucial position in the development and progression of breast cancer microenvironment. The purpose of our study was to identify immunogenic prognostic marker and explore potential regulatory mechanisms for breast cancer. We identified...

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Autores principales: Yang, Yan, He, Xin, Tang, Qian-Qian, Shao, You-Cheng, Song, Wen-Jing, Gong, Peng-Ju, Zeng, Yi-Fan, Huang, Si-Rui, Zhou, Jiang-Yao, Wan, Hui-Fang, Wei, Lei, Zhang, Jing-Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343142/
https://www.ncbi.nlm.nih.gov/pubmed/34367945
http://dx.doi.org/10.3389/fonc.2021.629633
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author Yang, Yan
He, Xin
Tang, Qian-Qian
Shao, You-Cheng
Song, Wen-Jing
Gong, Peng-Ju
Zeng, Yi-Fan
Huang, Si-Rui
Zhou, Jiang-Yao
Wan, Hui-Fang
Wei, Lei
Zhang, Jing-Wei
author_facet Yang, Yan
He, Xin
Tang, Qian-Qian
Shao, You-Cheng
Song, Wen-Jing
Gong, Peng-Ju
Zeng, Yi-Fan
Huang, Si-Rui
Zhou, Jiang-Yao
Wan, Hui-Fang
Wei, Lei
Zhang, Jing-Wei
author_sort Yang, Yan
collection PubMed
description A growing amount of evidence has indicated immune genes perform a crucial position in the development and progression of breast cancer microenvironment. The purpose of our study was to identify immunogenic prognostic marker and explore potential regulatory mechanisms for breast cancer. We identified the genes related to ImmuneScore using ESTIMATE algorithm and WGCNA analysis, and we identified the differentially expressed gene (DEGs). Then, Glia maturation factor γ (GMFG) was determined as a predictive factor by intersecting immune-related genes with DEGs and survival analysis. We found the expression of GMFG was lower in breast cancer tissues compared with normal breast tissues, which was further verified by immunohistochemical (IHC). Moreover, the decreased expression of GMFG was significantly related to the poor prognosis. Besides, the expression of GMFG was related to the age, ER status, PR status, HER2 status and tumor size, which further suggested that the expression of GMFG was correlated with the subtype and the growth of tumor. The univariate and multivariate Cox regression analyses revealed that age, stage, the expression level of GMFG and radiotherapy were independent factors for predicting the prognosis of breast cancer patients. Subsequently, a prognostic model to predict the 3-year, 5-year and 10-year overall survival rate was developed based on the above four variables, and visualized as a nomogram. The values of area under the curve of the nomogram at 3-year, 5-year and 10-year were 0.897, 0.873 and 0.922, respectively, which was higher than stage in prognostic accuracy. In addition, we also found that GMFG expression level was correlated with sensitivity of some breast cancer chemotherapy drugs. Furthermore, the results of GSEA indicated immune-related pathways were mainly enriched in GMFG-high-expression group. CIBERSORT analysis for the proportion of tumor-infiltrating immune cells (TIICs) suggested that expression of GMFG was positively association with multiple kinds T-cell in BC. Among them, CD8+ T cells had the strongest correlation with GMFG expression, which revealed that GMFG might has an antitumor effect by increasing the infiltration of CD8+ T cells in breast cancer. Accordingly, GMFG has the potential to become a novel immune biomarker for the diagnosis and treatment of breast cancer.
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spelling pubmed-83431422021-08-07 GMFG Has Potential to Be a Novel Prognostic Marker and Related to Immune Infiltrates in Breast Cancer Yang, Yan He, Xin Tang, Qian-Qian Shao, You-Cheng Song, Wen-Jing Gong, Peng-Ju Zeng, Yi-Fan Huang, Si-Rui Zhou, Jiang-Yao Wan, Hui-Fang Wei, Lei Zhang, Jing-Wei Front Oncol Oncology A growing amount of evidence has indicated immune genes perform a crucial position in the development and progression of breast cancer microenvironment. The purpose of our study was to identify immunogenic prognostic marker and explore potential regulatory mechanisms for breast cancer. We identified the genes related to ImmuneScore using ESTIMATE algorithm and WGCNA analysis, and we identified the differentially expressed gene (DEGs). Then, Glia maturation factor γ (GMFG) was determined as a predictive factor by intersecting immune-related genes with DEGs and survival analysis. We found the expression of GMFG was lower in breast cancer tissues compared with normal breast tissues, which was further verified by immunohistochemical (IHC). Moreover, the decreased expression of GMFG was significantly related to the poor prognosis. Besides, the expression of GMFG was related to the age, ER status, PR status, HER2 status and tumor size, which further suggested that the expression of GMFG was correlated with the subtype and the growth of tumor. The univariate and multivariate Cox regression analyses revealed that age, stage, the expression level of GMFG and radiotherapy were independent factors for predicting the prognosis of breast cancer patients. Subsequently, a prognostic model to predict the 3-year, 5-year and 10-year overall survival rate was developed based on the above four variables, and visualized as a nomogram. The values of area under the curve of the nomogram at 3-year, 5-year and 10-year were 0.897, 0.873 and 0.922, respectively, which was higher than stage in prognostic accuracy. In addition, we also found that GMFG expression level was correlated with sensitivity of some breast cancer chemotherapy drugs. Furthermore, the results of GSEA indicated immune-related pathways were mainly enriched in GMFG-high-expression group. CIBERSORT analysis for the proportion of tumor-infiltrating immune cells (TIICs) suggested that expression of GMFG was positively association with multiple kinds T-cell in BC. Among them, CD8+ T cells had the strongest correlation with GMFG expression, which revealed that GMFG might has an antitumor effect by increasing the infiltration of CD8+ T cells in breast cancer. Accordingly, GMFG has the potential to become a novel immune biomarker for the diagnosis and treatment of breast cancer. Frontiers Media S.A. 2021-07-23 /pmc/articles/PMC8343142/ /pubmed/34367945 http://dx.doi.org/10.3389/fonc.2021.629633 Text en Copyright © 2021 Yang, He, Tang, Shao, Song, Gong, Zeng, Huang, Zhou, Wan, Wei and Zhang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Yang, Yan
He, Xin
Tang, Qian-Qian
Shao, You-Cheng
Song, Wen-Jing
Gong, Peng-Ju
Zeng, Yi-Fan
Huang, Si-Rui
Zhou, Jiang-Yao
Wan, Hui-Fang
Wei, Lei
Zhang, Jing-Wei
GMFG Has Potential to Be a Novel Prognostic Marker and Related to Immune Infiltrates in Breast Cancer
title GMFG Has Potential to Be a Novel Prognostic Marker and Related to Immune Infiltrates in Breast Cancer
title_full GMFG Has Potential to Be a Novel Prognostic Marker and Related to Immune Infiltrates in Breast Cancer
title_fullStr GMFG Has Potential to Be a Novel Prognostic Marker and Related to Immune Infiltrates in Breast Cancer
title_full_unstemmed GMFG Has Potential to Be a Novel Prognostic Marker and Related to Immune Infiltrates in Breast Cancer
title_short GMFG Has Potential to Be a Novel Prognostic Marker and Related to Immune Infiltrates in Breast Cancer
title_sort gmfg has potential to be a novel prognostic marker and related to immune infiltrates in breast cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343142/
https://www.ncbi.nlm.nih.gov/pubmed/34367945
http://dx.doi.org/10.3389/fonc.2021.629633
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