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Systematic analyses of the role of prognostic and immunological EIF3A, a reader protein, in clear cell renal cell carcinoma

BACKGROUND: Eukaryotic initiation factor 3a (EIF3A), a “reader” protein for RNA methylation, has been found to be involved in promoting tumorigenesis in a variety of cancers. The impact of EIF3A in clear cell renal cell carcinoma (ccRCC) has yet to be reported. This study aimed to identify the progn...

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Autores principales: Zhang, Yi, Hua, Xiaoliang, Shi, Haoqiang, Zhang, Li, Xiao, Haibing, Liang, Chaozhao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8684683/
https://www.ncbi.nlm.nih.gov/pubmed/34923969
http://dx.doi.org/10.1186/s12935-021-02364-2
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author Zhang, Yi
Hua, Xiaoliang
Shi, Haoqiang
Zhang, Li
Xiao, Haibing
Liang, Chaozhao
author_facet Zhang, Yi
Hua, Xiaoliang
Shi, Haoqiang
Zhang, Li
Xiao, Haibing
Liang, Chaozhao
author_sort Zhang, Yi
collection PubMed
description BACKGROUND: Eukaryotic initiation factor 3a (EIF3A), a “reader” protein for RNA methylation, has been found to be involved in promoting tumorigenesis in a variety of cancers. The impact of EIF3A in clear cell renal cell carcinoma (ccRCC) has yet to be reported. This study aimed to identify the prognostic value of EIF3A in ccRCC and investigate the relationship between EIF3A expression and immune infiltration. METHODS: We collected 29 m6A-related mRNA data and clinicopathological parameters from The Cancer Genome Atlas (TCGA) database. Logistic regression analyses were used to analyse the correlation between EIF3A expression and clinical characteristics. Immunohistochemistry (IHC) was applied to examine EIF3A levels in normal and ccRCC tissues. Univariate and multivariate analyses were conducted to recognize independent factors associated with overall survival (OS) and disease-free survival (DFS). The nomogram aimed to predict the 1-, 3- and 5-year survival probabilities. Gene set enrichment analysis (GSEA) was carried out to determine the potential functions and related signalling pathways of EIF3A expression. To investigate EIF3A of coexpressed genes, we used LinkedOmics, and the results were subjected to enrichment analysis. Simultaneously, LinkedOmics and STRING datasets were used to identify EIF3A coexpressed genes that were visualized via Cytoscape. Finally, we evaluated whether EIF3A expression correlated with the infiltration of immune cells and the expression of marker genes in ccRCC by Tumour Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA). RESULT: EIF3A expression was significantly different between ccRCC tissues and normal tissues. EIF3A expression was correlated with poor prognostic clinicopathological factors, and K–M analyses revealed that low EIF3A expression was correlated with a poor prognosis. The results of univariate and multivariate analyses proved that EIF3A was a prognostic factor in ccRCC patients. GSEA results indicated that EIF3A high expression was enriched in the renal cell carcinoma pathway. EIF3A expression was significantly positively correlated with B cells, CD8 + T cells, CD4 + T cells, neutrophils, macrophages, and dendritic cells. Furthermore, EIF3A expression was associated with most marker genes of immune cells. CONCLUSIONS: EIF3A could serve as a potential biomarker for prognostic and diagnostic stratification of ccRCC and is related to immune cell infiltrates. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-02364-2.
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spelling pubmed-86846832021-12-20 Systematic analyses of the role of prognostic and immunological EIF3A, a reader protein, in clear cell renal cell carcinoma Zhang, Yi Hua, Xiaoliang Shi, Haoqiang Zhang, Li Xiao, Haibing Liang, Chaozhao Cancer Cell Int Primary Research BACKGROUND: Eukaryotic initiation factor 3a (EIF3A), a “reader” protein for RNA methylation, has been found to be involved in promoting tumorigenesis in a variety of cancers. The impact of EIF3A in clear cell renal cell carcinoma (ccRCC) has yet to be reported. This study aimed to identify the prognostic value of EIF3A in ccRCC and investigate the relationship between EIF3A expression and immune infiltration. METHODS: We collected 29 m6A-related mRNA data and clinicopathological parameters from The Cancer Genome Atlas (TCGA) database. Logistic regression analyses were used to analyse the correlation between EIF3A expression and clinical characteristics. Immunohistochemistry (IHC) was applied to examine EIF3A levels in normal and ccRCC tissues. Univariate and multivariate analyses were conducted to recognize independent factors associated with overall survival (OS) and disease-free survival (DFS). The nomogram aimed to predict the 1-, 3- and 5-year survival probabilities. Gene set enrichment analysis (GSEA) was carried out to determine the potential functions and related signalling pathways of EIF3A expression. To investigate EIF3A of coexpressed genes, we used LinkedOmics, and the results were subjected to enrichment analysis. Simultaneously, LinkedOmics and STRING datasets were used to identify EIF3A coexpressed genes that were visualized via Cytoscape. Finally, we evaluated whether EIF3A expression correlated with the infiltration of immune cells and the expression of marker genes in ccRCC by Tumour Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA). RESULT: EIF3A expression was significantly different between ccRCC tissues and normal tissues. EIF3A expression was correlated with poor prognostic clinicopathological factors, and K–M analyses revealed that low EIF3A expression was correlated with a poor prognosis. The results of univariate and multivariate analyses proved that EIF3A was a prognostic factor in ccRCC patients. GSEA results indicated that EIF3A high expression was enriched in the renal cell carcinoma pathway. EIF3A expression was significantly positively correlated with B cells, CD8 + T cells, CD4 + T cells, neutrophils, macrophages, and dendritic cells. Furthermore, EIF3A expression was associated with most marker genes of immune cells. CONCLUSIONS: EIF3A could serve as a potential biomarker for prognostic and diagnostic stratification of ccRCC and is related to immune cell infiltrates. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-02364-2. BioMed Central 2021-12-19 /pmc/articles/PMC8684683/ /pubmed/34923969 http://dx.doi.org/10.1186/s12935-021-02364-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://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
Zhang, Yi
Hua, Xiaoliang
Shi, Haoqiang
Zhang, Li
Xiao, Haibing
Liang, Chaozhao
Systematic analyses of the role of prognostic and immunological EIF3A, a reader protein, in clear cell renal cell carcinoma
title Systematic analyses of the role of prognostic and immunological EIF3A, a reader protein, in clear cell renal cell carcinoma
title_full Systematic analyses of the role of prognostic and immunological EIF3A, a reader protein, in clear cell renal cell carcinoma
title_fullStr Systematic analyses of the role of prognostic and immunological EIF3A, a reader protein, in clear cell renal cell carcinoma
title_full_unstemmed Systematic analyses of the role of prognostic and immunological EIF3A, a reader protein, in clear cell renal cell carcinoma
title_short Systematic analyses of the role of prognostic and immunological EIF3A, a reader protein, in clear cell renal cell carcinoma
title_sort systematic analyses of the role of prognostic and immunological eif3a, a reader protein, in clear cell renal cell carcinoma
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8684683/
https://www.ncbi.nlm.nih.gov/pubmed/34923969
http://dx.doi.org/10.1186/s12935-021-02364-2
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