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Construction of an endoplasmic reticulum stress-related signature in lung adenocarcinoma by comprehensive bioinformatics analysis
BACKGROUND: Lung Adenocarcinoma (LUAD) is a major component of lung cancer. Endoplasmic reticulum stress (ERS) has emerged as a new target for some tumor treatments. METHODS: The expression and clinical data of LUAD samples were downloaded from The Cancer Genome Atlas (TCGA) and The Gene Expression...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10186720/ https://www.ncbi.nlm.nih.gov/pubmed/37189138 http://dx.doi.org/10.1186/s12890-023-02443-2 |
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author | Wang, Yang Nie, Jun Dai, Ling Hu, Weiheng Han, Sen Zhang, Jie Chen, Xiaoling Ma, Xiangjuan Tian, Guangming Wu, Di Zhang, Ziran Long, Jieran Fang, Jian |
author_facet | Wang, Yang Nie, Jun Dai, Ling Hu, Weiheng Han, Sen Zhang, Jie Chen, Xiaoling Ma, Xiangjuan Tian, Guangming Wu, Di Zhang, Ziran Long, Jieran Fang, Jian |
author_sort | Wang, Yang |
collection | PubMed |
description | BACKGROUND: Lung Adenocarcinoma (LUAD) is a major component of lung cancer. Endoplasmic reticulum stress (ERS) has emerged as a new target for some tumor treatments. METHODS: The expression and clinical data of LUAD samples were downloaded from The Cancer Genome Atlas (TCGA) and The Gene Expression Omnibus (GEO) database, followed by acquiring ERS-related genes (ERSGs) from the GeneCards database. Differentially expressed endoplasmic reticulum stress-related genes (DE-ERSGs) were screened and used to construct a risk model by Cox regression analysis. Kaplan–Meier (K-M) curves and receiver operating characteristic (ROC) curves were plotted to determine the risk validity of the model. Moreover, enrichment analysis of differentially expressed genes (DEGs) between the high- and low- risk groups was conducted to investigate the functions related to the risk model. Furthermore, the differences in ERS status, vascular-related genes, tumor mutation burden (TMB), immunotherapy response, chemotherapy drug sensitivity and other indicators between the high- and low- risk groups were studied. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the mRNA expression levels of prognostic model genes. RESULTS: A total of 81 DE-ERSGs were identified in the TCGA-LUAD dataset, and a risk model, including HSPD1, PCSK9, GRIA1, MAOB, COL1A1, and CAV1, was constructed by Cox regression analysis. K-M and ROC analyses showed that the high-risk group had a low survival, and the Area Under Curve (AUC) of ROC curves of 1-, 3- and 5-years overall survival was all greater than 0.6. In addition, functional enrichment analysis suggested that the risk model was related to collagen and extracellular matrix. Furthermore, differential analysis showed vascular-related genes FLT1, TMB, neoantigen, PD-L1 protein (CD274), Tumor Immune Dysfunction and Exclusion (TIDE), and T cell exclusion score were significantly different between the high- and low-risk groups. Finally, qRT-PCR results showed that the mRNA expression levels of 6 prognostic genes were consistent with the analysis. CONCLUSION: A novel ERS-related risk model, including HSPD1, PCSK9, GRIA1, MAOB, COL1A1, and CAV1, was developed and validated, which provided a theoretical basis and reference value for ERS-related fields in the study and treatment of LUAD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12890-023-02443-2. |
format | Online Article Text |
id | pubmed-10186720 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-101867202023-05-17 Construction of an endoplasmic reticulum stress-related signature in lung adenocarcinoma by comprehensive bioinformatics analysis Wang, Yang Nie, Jun Dai, Ling Hu, Weiheng Han, Sen Zhang, Jie Chen, Xiaoling Ma, Xiangjuan Tian, Guangming Wu, Di Zhang, Ziran Long, Jieran Fang, Jian BMC Pulm Med Research BACKGROUND: Lung Adenocarcinoma (LUAD) is a major component of lung cancer. Endoplasmic reticulum stress (ERS) has emerged as a new target for some tumor treatments. METHODS: The expression and clinical data of LUAD samples were downloaded from The Cancer Genome Atlas (TCGA) and The Gene Expression Omnibus (GEO) database, followed by acquiring ERS-related genes (ERSGs) from the GeneCards database. Differentially expressed endoplasmic reticulum stress-related genes (DE-ERSGs) were screened and used to construct a risk model by Cox regression analysis. Kaplan–Meier (K-M) curves and receiver operating characteristic (ROC) curves were plotted to determine the risk validity of the model. Moreover, enrichment analysis of differentially expressed genes (DEGs) between the high- and low- risk groups was conducted to investigate the functions related to the risk model. Furthermore, the differences in ERS status, vascular-related genes, tumor mutation burden (TMB), immunotherapy response, chemotherapy drug sensitivity and other indicators between the high- and low- risk groups were studied. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the mRNA expression levels of prognostic model genes. RESULTS: A total of 81 DE-ERSGs were identified in the TCGA-LUAD dataset, and a risk model, including HSPD1, PCSK9, GRIA1, MAOB, COL1A1, and CAV1, was constructed by Cox regression analysis. K-M and ROC analyses showed that the high-risk group had a low survival, and the Area Under Curve (AUC) of ROC curves of 1-, 3- and 5-years overall survival was all greater than 0.6. In addition, functional enrichment analysis suggested that the risk model was related to collagen and extracellular matrix. Furthermore, differential analysis showed vascular-related genes FLT1, TMB, neoantigen, PD-L1 protein (CD274), Tumor Immune Dysfunction and Exclusion (TIDE), and T cell exclusion score were significantly different between the high- and low-risk groups. Finally, qRT-PCR results showed that the mRNA expression levels of 6 prognostic genes were consistent with the analysis. CONCLUSION: A novel ERS-related risk model, including HSPD1, PCSK9, GRIA1, MAOB, COL1A1, and CAV1, was developed and validated, which provided a theoretical basis and reference value for ERS-related fields in the study and treatment of LUAD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12890-023-02443-2. BioMed Central 2023-05-15 /pmc/articles/PMC10186720/ /pubmed/37189138 http://dx.doi.org/10.1186/s12890-023-02443-2 Text en © The Author(s) 2023 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 Wang, Yang Nie, Jun Dai, Ling Hu, Weiheng Han, Sen Zhang, Jie Chen, Xiaoling Ma, Xiangjuan Tian, Guangming Wu, Di Zhang, Ziran Long, Jieran Fang, Jian Construction of an endoplasmic reticulum stress-related signature in lung adenocarcinoma by comprehensive bioinformatics analysis |
title | Construction of an endoplasmic reticulum stress-related signature in lung adenocarcinoma by comprehensive bioinformatics analysis |
title_full | Construction of an endoplasmic reticulum stress-related signature in lung adenocarcinoma by comprehensive bioinformatics analysis |
title_fullStr | Construction of an endoplasmic reticulum stress-related signature in lung adenocarcinoma by comprehensive bioinformatics analysis |
title_full_unstemmed | Construction of an endoplasmic reticulum stress-related signature in lung adenocarcinoma by comprehensive bioinformatics analysis |
title_short | Construction of an endoplasmic reticulum stress-related signature in lung adenocarcinoma by comprehensive bioinformatics analysis |
title_sort | construction of an endoplasmic reticulum stress-related signature in lung adenocarcinoma by comprehensive bioinformatics analysis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10186720/ https://www.ncbi.nlm.nih.gov/pubmed/37189138 http://dx.doi.org/10.1186/s12890-023-02443-2 |
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