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Tumor mutation burden in connection with immune-related survival in uterine corpus endometrial carcinoma

BACKGROUND: UCEC is the most common gynecological malignancy in many countries, and its mechanism of occurrence and development is related to tumor mutation burden (TMB) and immune cell infiltration. Therefore, it is necessary to systematically explore the TMB-related gene profile in immune cells to...

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Autores principales: Zhao, Ling, Fu, Xueshu, Han, Xiling, Yu, Yanjun, Ye, Yaping, Gao, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842022/
https://www.ncbi.nlm.nih.gov/pubmed/33509222
http://dx.doi.org/10.1186/s12935-021-01774-6
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author Zhao, Ling
Fu, Xueshu
Han, Xiling
Yu, Yanjun
Ye, Yaping
Gao, Jun
author_facet Zhao, Ling
Fu, Xueshu
Han, Xiling
Yu, Yanjun
Ye, Yaping
Gao, Jun
author_sort Zhao, Ling
collection PubMed
description BACKGROUND: UCEC is the most common gynecological malignancy in many countries, and its mechanism of occurrence and development is related to tumor mutation burden (TMB) and immune cell infiltration. Therefore, it is necessary to systematically explore the TMB-related gene profile in immune cells to improve the prognosis of UCEC. METHODS: We integrated TMB-related genes with basic clinical information of UCEC patients based on TCGA dataset. Differentially expressed genes (DEGs) were selected through differential expression screening, PPI, and enrichment analysis. Additionally, we analyzed the components of immune cell infiltration of the DEGs to obtain the differential immunity-related genes. A single factor and multifactor Cox regression analyses were conducted to establish new prognostic indicators of OS and DFS based on TMB-related immune genes. To further study the correlation between survival and immune cell infiltration, a Cox model based on these immune infiltration compositions was built. Using the clinical variables, we established nomograms for OS and DFS. RESULTS: 393 DEGs were significantly associated with clinical outcomes and the immune component in patients with UCEC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes, Genomes (KEGG) pathway and protein-protein interaction network (PPI) analyses revealed the role of these genes and information on related pathways. Then, two prognostic models were established based on the differential immune genes for OS (GFAP and MX2) and DFS (MX2, GFAP, IGHM, FGF20, and TRAV21). In DFS, the differential immune genes were related to CD4+ T cell, CD8+ T cell, macrophage, and neutrophil (all P < 0.05). B cell and CD8+ T cell were independent prognostic factors from among the immune cell elements in UCEC. Finally, the risk scores of these models were combined with the clinical elements-based nomogram models, and the AUC values were all over 0.7. CONCLUSIONS: Our results identified several clinically significant differential immune genes and established relevant prognostic models, providing a basis for the molecular analysis of TMB and immune cells in UCEC, and identified potential prognostic and immune-related genes for UCEC. We added clinical related conditions for further analysis to confirm the identity of the genes and clinical elements-based models.
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spelling pubmed-78420222021-01-28 Tumor mutation burden in connection with immune-related survival in uterine corpus endometrial carcinoma Zhao, Ling Fu, Xueshu Han, Xiling Yu, Yanjun Ye, Yaping Gao, Jun Cancer Cell Int Primary Research BACKGROUND: UCEC is the most common gynecological malignancy in many countries, and its mechanism of occurrence and development is related to tumor mutation burden (TMB) and immune cell infiltration. Therefore, it is necessary to systematically explore the TMB-related gene profile in immune cells to improve the prognosis of UCEC. METHODS: We integrated TMB-related genes with basic clinical information of UCEC patients based on TCGA dataset. Differentially expressed genes (DEGs) were selected through differential expression screening, PPI, and enrichment analysis. Additionally, we analyzed the components of immune cell infiltration of the DEGs to obtain the differential immunity-related genes. A single factor and multifactor Cox regression analyses were conducted to establish new prognostic indicators of OS and DFS based on TMB-related immune genes. To further study the correlation between survival and immune cell infiltration, a Cox model based on these immune infiltration compositions was built. Using the clinical variables, we established nomograms for OS and DFS. RESULTS: 393 DEGs were significantly associated with clinical outcomes and the immune component in patients with UCEC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes, Genomes (KEGG) pathway and protein-protein interaction network (PPI) analyses revealed the role of these genes and information on related pathways. Then, two prognostic models were established based on the differential immune genes for OS (GFAP and MX2) and DFS (MX2, GFAP, IGHM, FGF20, and TRAV21). In DFS, the differential immune genes were related to CD4+ T cell, CD8+ T cell, macrophage, and neutrophil (all P < 0.05). B cell and CD8+ T cell were independent prognostic factors from among the immune cell elements in UCEC. Finally, the risk scores of these models were combined with the clinical elements-based nomogram models, and the AUC values were all over 0.7. CONCLUSIONS: Our results identified several clinically significant differential immune genes and established relevant prognostic models, providing a basis for the molecular analysis of TMB and immune cells in UCEC, and identified potential prognostic and immune-related genes for UCEC. We added clinical related conditions for further analysis to confirm the identity of the genes and clinical elements-based models. BioMed Central 2021-01-28 /pmc/articles/PMC7842022/ /pubmed/33509222 http://dx.doi.org/10.1186/s12935-021-01774-6 Text en © The Author(s) 2021 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/. 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 in a credit line to the data.
spellingShingle Primary Research
Zhao, Ling
Fu, Xueshu
Han, Xiling
Yu, Yanjun
Ye, Yaping
Gao, Jun
Tumor mutation burden in connection with immune-related survival in uterine corpus endometrial carcinoma
title Tumor mutation burden in connection with immune-related survival in uterine corpus endometrial carcinoma
title_full Tumor mutation burden in connection with immune-related survival in uterine corpus endometrial carcinoma
title_fullStr Tumor mutation burden in connection with immune-related survival in uterine corpus endometrial carcinoma
title_full_unstemmed Tumor mutation burden in connection with immune-related survival in uterine corpus endometrial carcinoma
title_short Tumor mutation burden in connection with immune-related survival in uterine corpus endometrial carcinoma
title_sort tumor mutation burden in connection with immune-related survival in uterine corpus endometrial carcinoma
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842022/
https://www.ncbi.nlm.nih.gov/pubmed/33509222
http://dx.doi.org/10.1186/s12935-021-01774-6
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