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An integrated analysis of prognostic and immune infiltrates for hub genes as potential survival indicators in patients with lung adenocarcinoma
OBJECTIVE: Lung adenocarcinoma (LUAD) is one of the major subtypes of lung cancer that is associated with poor prognosis. The aim of this study was to identify useful biomarkers to enhance the treatment and diagnosis of LUAD. METHODS: GEO2R was used to identify common up-regulated differentially exp...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8966338/ https://www.ncbi.nlm.nih.gov/pubmed/35354488 http://dx.doi.org/10.1186/s12957-022-02543-z |
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author | Xu, Zhiyun Wang, Shi Ren, Zhijian Gao, Xiang Xu, Lin Zhang, Shuai Ren, Binhui |
author_facet | Xu, Zhiyun Wang, Shi Ren, Zhijian Gao, Xiang Xu, Lin Zhang, Shuai Ren, Binhui |
author_sort | Xu, Zhiyun |
collection | PubMed |
description | OBJECTIVE: Lung adenocarcinoma (LUAD) is one of the major subtypes of lung cancer that is associated with poor prognosis. The aim of this study was to identify useful biomarkers to enhance the treatment and diagnosis of LUAD. METHODS: GEO2R was used to identify common up-regulated differentially expressed genes (DEGs) in the GSE32863, GSE40791, and GSE75037 datasets. The DEGs were submitted to Metascape for gene ontology and pathway enrichment analysis as well as construction of the protein-protein interaction (PPI) network, while the molecular complex detection (MCODE) plug-in was employed to filter important subnetworks. The expression levels of the hub genes and their prognostic values were evaluated using the UALCAN, GEPIA2, and Kaplan-Meier plotter databases. The timer algorithm was utilized to determine the correlation between immune cell infiltration and the expression levels of hub genes in LUAD tissues. In addition, the hub gene mutation landscape and the correlation analysis with tumor mutational burden (TMB) score were evaluated using maftools package and ggstatsplot package in R software, respectively. RESULTS: We identified 156 common up-regulated DEGs, with gene ontology and pathway enrichment analysis indicating that they were mostly enriched in mitotic cell cycle process and cell cycle pathway. DEGs in the subnetwork with the largest number of genes were AURKB, CCNB2, CDC20, CDCA5, CDCA8, CENPF, and KNTC1. The seven hub genes were highly expressed in LUAD tissues and were associated with poor prognosis. These hub genes were negatively correlated with most immune cells. The somatic mutation landscape showed that AURKB, CDC20, CENPF, and KNTC1 had mutations and were positively correlated with TMB scores. CONCLUSIONS: Our findings demonstrate that increased expression of seven hub genes is associated with poor prognosis for LUAD patients. Additionally, the TMB score indicates that the high expression of hub gene increases immune cell infiltration in patients with lung adenocarcinoma which may significantly improve response to immunotherapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12957-022-02543-z. |
format | Online Article Text |
id | pubmed-8966338 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-89663382022-03-31 An integrated analysis of prognostic and immune infiltrates for hub genes as potential survival indicators in patients with lung adenocarcinoma Xu, Zhiyun Wang, Shi Ren, Zhijian Gao, Xiang Xu, Lin Zhang, Shuai Ren, Binhui World J Surg Oncol Research OBJECTIVE: Lung adenocarcinoma (LUAD) is one of the major subtypes of lung cancer that is associated with poor prognosis. The aim of this study was to identify useful biomarkers to enhance the treatment and diagnosis of LUAD. METHODS: GEO2R was used to identify common up-regulated differentially expressed genes (DEGs) in the GSE32863, GSE40791, and GSE75037 datasets. The DEGs were submitted to Metascape for gene ontology and pathway enrichment analysis as well as construction of the protein-protein interaction (PPI) network, while the molecular complex detection (MCODE) plug-in was employed to filter important subnetworks. The expression levels of the hub genes and their prognostic values were evaluated using the UALCAN, GEPIA2, and Kaplan-Meier plotter databases. The timer algorithm was utilized to determine the correlation between immune cell infiltration and the expression levels of hub genes in LUAD tissues. In addition, the hub gene mutation landscape and the correlation analysis with tumor mutational burden (TMB) score were evaluated using maftools package and ggstatsplot package in R software, respectively. RESULTS: We identified 156 common up-regulated DEGs, with gene ontology and pathway enrichment analysis indicating that they were mostly enriched in mitotic cell cycle process and cell cycle pathway. DEGs in the subnetwork with the largest number of genes were AURKB, CCNB2, CDC20, CDCA5, CDCA8, CENPF, and KNTC1. The seven hub genes were highly expressed in LUAD tissues and were associated with poor prognosis. These hub genes were negatively correlated with most immune cells. The somatic mutation landscape showed that AURKB, CDC20, CENPF, and KNTC1 had mutations and were positively correlated with TMB scores. CONCLUSIONS: Our findings demonstrate that increased expression of seven hub genes is associated with poor prognosis for LUAD patients. Additionally, the TMB score indicates that the high expression of hub gene increases immune cell infiltration in patients with lung adenocarcinoma which may significantly improve response to immunotherapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12957-022-02543-z. BioMed Central 2022-03-30 /pmc/articles/PMC8966338/ /pubmed/35354488 http://dx.doi.org/10.1186/s12957-022-02543-z Text en © The Author(s) 2022 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 | Research Xu, Zhiyun Wang, Shi Ren, Zhijian Gao, Xiang Xu, Lin Zhang, Shuai Ren, Binhui An integrated analysis of prognostic and immune infiltrates for hub genes as potential survival indicators in patients with lung adenocarcinoma |
title | An integrated analysis of prognostic and immune infiltrates for hub genes as potential survival indicators in patients with lung adenocarcinoma |
title_full | An integrated analysis of prognostic and immune infiltrates for hub genes as potential survival indicators in patients with lung adenocarcinoma |
title_fullStr | An integrated analysis of prognostic and immune infiltrates for hub genes as potential survival indicators in patients with lung adenocarcinoma |
title_full_unstemmed | An integrated analysis of prognostic and immune infiltrates for hub genes as potential survival indicators in patients with lung adenocarcinoma |
title_short | An integrated analysis of prognostic and immune infiltrates for hub genes as potential survival indicators in patients with lung adenocarcinoma |
title_sort | integrated analysis of prognostic and immune infiltrates for hub genes as potential survival indicators in patients with lung adenocarcinoma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8966338/ https://www.ncbi.nlm.nih.gov/pubmed/35354488 http://dx.doi.org/10.1186/s12957-022-02543-z |
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