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Identification of 3 subpopulations of tumor-infiltrating immune cells for malignant transformation of low-grade glioma

BACKGROUND: Tumor-infiltrating immune cells (TIICs) are highly relevant to clinical outcome of glioma. However, previous studies cannot account for the diverse functions that make up the immune response in malignant transformation (MT) from low-grade glioma (LGG) to high-grade glioma (HGG). METHODS:...

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Autores principales: Lu, Jiacheng, Li, Hailin, Chen, Zhengxin, Fan, Ligang, Feng, Shuang, Cai, Xiaomin, Wang, Huibo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788075/
https://www.ncbi.nlm.nih.gov/pubmed/31632199
http://dx.doi.org/10.1186/s12935-019-0972-1
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author Lu, Jiacheng
Li, Hailin
Chen, Zhengxin
Fan, Ligang
Feng, Shuang
Cai, Xiaomin
Wang, Huibo
author_facet Lu, Jiacheng
Li, Hailin
Chen, Zhengxin
Fan, Ligang
Feng, Shuang
Cai, Xiaomin
Wang, Huibo
author_sort Lu, Jiacheng
collection PubMed
description BACKGROUND: Tumor-infiltrating immune cells (TIICs) are highly relevant to clinical outcome of glioma. However, previous studies cannot account for the diverse functions that make up the immune response in malignant transformation (MT) from low-grade glioma (LGG) to high-grade glioma (HGG). METHODS: Transcriptome level, genomic profiles and its relationship with clinical practice were obtained from TCGA and CGGA database. The “Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT)” algorithm was used to estimate the fraction of 22 immune cell types. We divided the TCGA and CGGA set into an experiment set (n = 174) and a validation set (n = 74) by random number table method. Univariate and multivariate analyses were performed to evaluate the 22 TIICs’ value for MT in LGG. ROC curve was plotted to calculate area under curve (AUC) and cut-off value. RESULTS: Heterogeneity between TIICs exists in both intra- and inter-groups. Several TIICs are notably associated with tumor grade, molecular subtypes and survival. T follicular helper (TFH) cells, activated NK Cells and M0 macrophages were screened out to be independent predictors for MT in LGG and formed an immune risk score (IRS) (AUC = 0.732, p < 0.001, 95% CI 0.657–0.808 cut-off value = 0.191). In addition, the IRS model was validated by validation group, Immunohistochemistry (IHC) and functional enrichment analyses. CONCLUSIONS: The proposed IRS model provides promising novel signatures for predicting MT from LGG to HGG and may bring a better design of glioma immunotherapy studies in years to come.
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spelling pubmed-67880752019-10-18 Identification of 3 subpopulations of tumor-infiltrating immune cells for malignant transformation of low-grade glioma Lu, Jiacheng Li, Hailin Chen, Zhengxin Fan, Ligang Feng, Shuang Cai, Xiaomin Wang, Huibo Cancer Cell Int Primary Research BACKGROUND: Tumor-infiltrating immune cells (TIICs) are highly relevant to clinical outcome of glioma. However, previous studies cannot account for the diverse functions that make up the immune response in malignant transformation (MT) from low-grade glioma (LGG) to high-grade glioma (HGG). METHODS: Transcriptome level, genomic profiles and its relationship with clinical practice were obtained from TCGA and CGGA database. The “Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT)” algorithm was used to estimate the fraction of 22 immune cell types. We divided the TCGA and CGGA set into an experiment set (n = 174) and a validation set (n = 74) by random number table method. Univariate and multivariate analyses were performed to evaluate the 22 TIICs’ value for MT in LGG. ROC curve was plotted to calculate area under curve (AUC) and cut-off value. RESULTS: Heterogeneity between TIICs exists in both intra- and inter-groups. Several TIICs are notably associated with tumor grade, molecular subtypes and survival. T follicular helper (TFH) cells, activated NK Cells and M0 macrophages were screened out to be independent predictors for MT in LGG and formed an immune risk score (IRS) (AUC = 0.732, p < 0.001, 95% CI 0.657–0.808 cut-off value = 0.191). In addition, the IRS model was validated by validation group, Immunohistochemistry (IHC) and functional enrichment analyses. CONCLUSIONS: The proposed IRS model provides promising novel signatures for predicting MT from LGG to HGG and may bring a better design of glioma immunotherapy studies in years to come. BioMed Central 2019-10-11 /pmc/articles/PMC6788075/ /pubmed/31632199 http://dx.doi.org/10.1186/s12935-019-0972-1 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Primary Research
Lu, Jiacheng
Li, Hailin
Chen, Zhengxin
Fan, Ligang
Feng, Shuang
Cai, Xiaomin
Wang, Huibo
Identification of 3 subpopulations of tumor-infiltrating immune cells for malignant transformation of low-grade glioma
title Identification of 3 subpopulations of tumor-infiltrating immune cells for malignant transformation of low-grade glioma
title_full Identification of 3 subpopulations of tumor-infiltrating immune cells for malignant transformation of low-grade glioma
title_fullStr Identification of 3 subpopulations of tumor-infiltrating immune cells for malignant transformation of low-grade glioma
title_full_unstemmed Identification of 3 subpopulations of tumor-infiltrating immune cells for malignant transformation of low-grade glioma
title_short Identification of 3 subpopulations of tumor-infiltrating immune cells for malignant transformation of low-grade glioma
title_sort identification of 3 subpopulations of tumor-infiltrating immune cells for malignant transformation of low-grade glioma
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788075/
https://www.ncbi.nlm.nih.gov/pubmed/31632199
http://dx.doi.org/10.1186/s12935-019-0972-1
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