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Identification of Key Genes Driving Tumor Associated Macrophage Migration and Polarization Based on Immune Fingerprints of Lung Adenocarcinoma

The identification of reliable indicators in the tumor microenvironment (TME) is critical for tumor prognosis. Tumor associated macrophages (TAMs) are the major component of non-tumor stromal cells in TME and have increasingly been recognized as a predictive biomarker for lung adenocarcinoma (LUAD)...

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Autores principales: Wu, Jing, Zhou, Jiawei, Xu, Qian, Foley, Ruth, Guo, Jianqiang, Zhang, Xin, Tian, Chang, Mu, Min, Xing, Yingru, Liu, Yafeng, Wang, Xueqin, Hu, Dong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600368/
https://www.ncbi.nlm.nih.gov/pubmed/34805160
http://dx.doi.org/10.3389/fcell.2021.751800
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author Wu, Jing
Zhou, Jiawei
Xu, Qian
Foley, Ruth
Guo, Jianqiang
Zhang, Xin
Tian, Chang
Mu, Min
Xing, Yingru
Liu, Yafeng
Wang, Xueqin
Hu, Dong
author_facet Wu, Jing
Zhou, Jiawei
Xu, Qian
Foley, Ruth
Guo, Jianqiang
Zhang, Xin
Tian, Chang
Mu, Min
Xing, Yingru
Liu, Yafeng
Wang, Xueqin
Hu, Dong
author_sort Wu, Jing
collection PubMed
description The identification of reliable indicators in the tumor microenvironment (TME) is critical for tumor prognosis. Tumor associated macrophages (TAMs) are the major component of non-tumor stromal cells in TME and have increasingly been recognized as a predictive biomarker for lung adenocarcinoma (LUAD) prognosis. Here, we report the development of a prognosis model for LUAD using three immune-related genes (IRGs) detected in The Cancer Genome Atlas (TCGA) which potentially regulate TAMs in TME. In 497 LUAD patients, higher immune scores conferred better overall survival (OS). We identified 93 hub IRGs out of 234 for further prognostic significance. Among them, three IRGs (BTK, Cd1c, and S100P) were proved to be closely correlated to the prognosis of patients with LUAD. Moreover, the immune risk score (IRS) based on the gene expression level of the three IRGs was an independent prognostic factor for OS. Higher IRS predicted lower OS, higher mortality and worse tumor stage. With a good predictive ability [area under the ROC curve (AUC) in TCGA = 0.701, AUC in GEO = 0.722], the IRS contributed to a good risk stratification ability of the nomogram. Immunologically, the three IRGs were related to M1 macrophages and NK cell subsets in TME. Interestingly, by characterizing these immune components in situ we found that S100P is a driver for tumor cells to induce TAM migration and M2 polarization in the immunosuppressive tumor niche. We identified the key genes driving TAM migration and transformation and elucidated the immune landscape of LUAD. The data suggest that IRGs from TME have the potential to become indicators for estimating cancer prognosis and guiding individualized treatment.
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spelling pubmed-86003682021-11-19 Identification of Key Genes Driving Tumor Associated Macrophage Migration and Polarization Based on Immune Fingerprints of Lung Adenocarcinoma Wu, Jing Zhou, Jiawei Xu, Qian Foley, Ruth Guo, Jianqiang Zhang, Xin Tian, Chang Mu, Min Xing, Yingru Liu, Yafeng Wang, Xueqin Hu, Dong Front Cell Dev Biol Cell and Developmental Biology The identification of reliable indicators in the tumor microenvironment (TME) is critical for tumor prognosis. Tumor associated macrophages (TAMs) are the major component of non-tumor stromal cells in TME and have increasingly been recognized as a predictive biomarker for lung adenocarcinoma (LUAD) prognosis. Here, we report the development of a prognosis model for LUAD using three immune-related genes (IRGs) detected in The Cancer Genome Atlas (TCGA) which potentially regulate TAMs in TME. In 497 LUAD patients, higher immune scores conferred better overall survival (OS). We identified 93 hub IRGs out of 234 for further prognostic significance. Among them, three IRGs (BTK, Cd1c, and S100P) were proved to be closely correlated to the prognosis of patients with LUAD. Moreover, the immune risk score (IRS) based on the gene expression level of the three IRGs was an independent prognostic factor for OS. Higher IRS predicted lower OS, higher mortality and worse tumor stage. With a good predictive ability [area under the ROC curve (AUC) in TCGA = 0.701, AUC in GEO = 0.722], the IRS contributed to a good risk stratification ability of the nomogram. Immunologically, the three IRGs were related to M1 macrophages and NK cell subsets in TME. Interestingly, by characterizing these immune components in situ we found that S100P is a driver for tumor cells to induce TAM migration and M2 polarization in the immunosuppressive tumor niche. We identified the key genes driving TAM migration and transformation and elucidated the immune landscape of LUAD. The data suggest that IRGs from TME have the potential to become indicators for estimating cancer prognosis and guiding individualized treatment. Frontiers Media S.A. 2021-11-04 /pmc/articles/PMC8600368/ /pubmed/34805160 http://dx.doi.org/10.3389/fcell.2021.751800 Text en Copyright © 2021 Wu, Zhou, Xu, Foley, Guo, Zhang, Tian, Mu, Xing, Liu, Wang and Hu. 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 Cell and Developmental Biology
Wu, Jing
Zhou, Jiawei
Xu, Qian
Foley, Ruth
Guo, Jianqiang
Zhang, Xin
Tian, Chang
Mu, Min
Xing, Yingru
Liu, Yafeng
Wang, Xueqin
Hu, Dong
Identification of Key Genes Driving Tumor Associated Macrophage Migration and Polarization Based on Immune Fingerprints of Lung Adenocarcinoma
title Identification of Key Genes Driving Tumor Associated Macrophage Migration and Polarization Based on Immune Fingerprints of Lung Adenocarcinoma
title_full Identification of Key Genes Driving Tumor Associated Macrophage Migration and Polarization Based on Immune Fingerprints of Lung Adenocarcinoma
title_fullStr Identification of Key Genes Driving Tumor Associated Macrophage Migration and Polarization Based on Immune Fingerprints of Lung Adenocarcinoma
title_full_unstemmed Identification of Key Genes Driving Tumor Associated Macrophage Migration and Polarization Based on Immune Fingerprints of Lung Adenocarcinoma
title_short Identification of Key Genes Driving Tumor Associated Macrophage Migration and Polarization Based on Immune Fingerprints of Lung Adenocarcinoma
title_sort identification of key genes driving tumor associated macrophage migration and polarization based on immune fingerprints of lung adenocarcinoma
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600368/
https://www.ncbi.nlm.nih.gov/pubmed/34805160
http://dx.doi.org/10.3389/fcell.2021.751800
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