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Construction of N-7 methylguanine-related mRNA prognostic model in uterine corpus endometrial carcinoma based on multi-omics data and immune-related analysis
N-7 methylguanine (m7G) is one of the most common RNA base modifications in post-transcriptional regulation, which participates in multiple processes such as transcription, mRNA splicing and translation during the mRNA life cycle. However, its expression and prognostic value in uterine corpus endome...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9637130/ https://www.ncbi.nlm.nih.gov/pubmed/36335189 http://dx.doi.org/10.1038/s41598-022-22879-6 |
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author | Zhao, Junde Zou, Jiani Jiao, Wenjian Lin, Lidong Wang, Jiuling Lin, Zhiheng |
author_facet | Zhao, Junde Zou, Jiani Jiao, Wenjian Lin, Lidong Wang, Jiuling Lin, Zhiheng |
author_sort | Zhao, Junde |
collection | PubMed |
description | N-7 methylguanine (m7G) is one of the most common RNA base modifications in post-transcriptional regulation, which participates in multiple processes such as transcription, mRNA splicing and translation during the mRNA life cycle. However, its expression and prognostic value in uterine corpus endometrial carcinoma (UCEC) have not been systematically studied. In this paper, the data such as gene expression profiles, clinical data of UCEC patients, somatic mutations and copy number variants (CNVs) are obtained from the cancer genome atlas (TCGA) and UCSC Xena. By analyzing the expression differences of m7G-related mRNA in UCEC and plotting the correlation network maps, a risk score model composed of four m7G-related mRNAs (NSUN2, NUDT3, LARP1 and NCBP3) is constructed using least absolute shrinkage and selection operator (LASSO), univariate and multivariate Cox regression in order to identify prognosis and immune response. The correlation of clinical prognosis is analyzed between the m7G-related mRNA and UCEC via Kaplan–Meier method, receiver operating characteristic (ROC) curve, principal component analysis (PCA), t-SNE, decision curve analysis (DCA) curve and nomogram etc. It is concluded that the high risk is significantly correlated with (P < 0.001) the poorer overall survival (OS) in patients with UCEC. It is one of the independent risk factors affecting the OS. Differentially expressed genes are identified by R software in the high and low risk groups. The functional analysis and pathway enrichment analysis have been performed. Single sample gene set enrichment analysis (ssGSEA), immune checkpoints, m6A-related genes, tumor mutation burden (TMB), stem cell correlation, tumor immune dysfunction and rejection (TIDE) scores and drug sensitivity are also used to study the risk model. In addition, we have obtained 3 genotypes based on consensus clustering, which are significantly related to (P < 0.001) the OS and progression-free survival (PFS). The deconvolution algorithm (CIBERSORT) is applied to calculate the proportion of 22 tumor infiltrating immune cells (TIC) in UCEC patients and the estimation algorithm (ESTIMATE) is applied to work out the number of immune and matrix components. In summary, m7G-related mRNA may become a potential biomarker for UCEC prognosis, which may promote UCEC occurrence and development by regulating cell cycles and immune cell infiltration. It is expected to become a potential therapeutic target of UECE. |
format | Online Article Text |
id | pubmed-9637130 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-96371302022-11-07 Construction of N-7 methylguanine-related mRNA prognostic model in uterine corpus endometrial carcinoma based on multi-omics data and immune-related analysis Zhao, Junde Zou, Jiani Jiao, Wenjian Lin, Lidong Wang, Jiuling Lin, Zhiheng Sci Rep Article N-7 methylguanine (m7G) is one of the most common RNA base modifications in post-transcriptional regulation, which participates in multiple processes such as transcription, mRNA splicing and translation during the mRNA life cycle. However, its expression and prognostic value in uterine corpus endometrial carcinoma (UCEC) have not been systematically studied. In this paper, the data such as gene expression profiles, clinical data of UCEC patients, somatic mutations and copy number variants (CNVs) are obtained from the cancer genome atlas (TCGA) and UCSC Xena. By analyzing the expression differences of m7G-related mRNA in UCEC and plotting the correlation network maps, a risk score model composed of four m7G-related mRNAs (NSUN2, NUDT3, LARP1 and NCBP3) is constructed using least absolute shrinkage and selection operator (LASSO), univariate and multivariate Cox regression in order to identify prognosis and immune response. The correlation of clinical prognosis is analyzed between the m7G-related mRNA and UCEC via Kaplan–Meier method, receiver operating characteristic (ROC) curve, principal component analysis (PCA), t-SNE, decision curve analysis (DCA) curve and nomogram etc. It is concluded that the high risk is significantly correlated with (P < 0.001) the poorer overall survival (OS) in patients with UCEC. It is one of the independent risk factors affecting the OS. Differentially expressed genes are identified by R software in the high and low risk groups. The functional analysis and pathway enrichment analysis have been performed. Single sample gene set enrichment analysis (ssGSEA), immune checkpoints, m6A-related genes, tumor mutation burden (TMB), stem cell correlation, tumor immune dysfunction and rejection (TIDE) scores and drug sensitivity are also used to study the risk model. In addition, we have obtained 3 genotypes based on consensus clustering, which are significantly related to (P < 0.001) the OS and progression-free survival (PFS). The deconvolution algorithm (CIBERSORT) is applied to calculate the proportion of 22 tumor infiltrating immune cells (TIC) in UCEC patients and the estimation algorithm (ESTIMATE) is applied to work out the number of immune and matrix components. In summary, m7G-related mRNA may become a potential biomarker for UCEC prognosis, which may promote UCEC occurrence and development by regulating cell cycles and immune cell infiltration. It is expected to become a potential therapeutic target of UECE. Nature Publishing Group UK 2022-11-05 /pmc/articles/PMC9637130/ /pubmed/36335189 http://dx.doi.org/10.1038/s41598-022-22879-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This 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/) . |
spellingShingle | Article Zhao, Junde Zou, Jiani Jiao, Wenjian Lin, Lidong Wang, Jiuling Lin, Zhiheng Construction of N-7 methylguanine-related mRNA prognostic model in uterine corpus endometrial carcinoma based on multi-omics data and immune-related analysis |
title | Construction of N-7 methylguanine-related mRNA prognostic model in uterine corpus endometrial carcinoma based on multi-omics data and immune-related analysis |
title_full | Construction of N-7 methylguanine-related mRNA prognostic model in uterine corpus endometrial carcinoma based on multi-omics data and immune-related analysis |
title_fullStr | Construction of N-7 methylguanine-related mRNA prognostic model in uterine corpus endometrial carcinoma based on multi-omics data and immune-related analysis |
title_full_unstemmed | Construction of N-7 methylguanine-related mRNA prognostic model in uterine corpus endometrial carcinoma based on multi-omics data and immune-related analysis |
title_short | Construction of N-7 methylguanine-related mRNA prognostic model in uterine corpus endometrial carcinoma based on multi-omics data and immune-related analysis |
title_sort | construction of n-7 methylguanine-related mrna prognostic model in uterine corpus endometrial carcinoma based on multi-omics data and immune-related analysis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9637130/ https://www.ncbi.nlm.nih.gov/pubmed/36335189 http://dx.doi.org/10.1038/s41598-022-22879-6 |
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