Development and Validation of a Prognostic N6-Methyladenosine-Related Immune Gene Signature for Lung Adenocarcinoma

Lemeng Zhang, Yongzhong Luo, Tianli Cheng, Jianhua Chen, Hua Yang, Xiaoping Wen, Zhou Jiang, Haitao Li, Changqie Pan Thoracic Medicine Department 1, Hunan Cancer Hospital, Changsha, Hunan Province, 410013, People’s Republic of ChinaCorrespondence: Yongzhong Luo Tel/Fax +86-731-89762220Email luoyongz...

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Auteurs principaux:	Zhang L, Luo Y, Cheng T, Chen J, Yang H, Wen X, Jiang Z, Li H, Pan C
Format:	article
Langue:	EN
Publié:	Dove Medical Press 2021
Sujets:	lung adenocarcinoma n6-methyladenosine methylation immune-related genes immune microenvironment prognostic signature Therapeutics. Pharmacology RM1-950
Accès en ligne:	https://doaj.org/article/be5a242b58dd4f45b8ccc803ecf5b2ad
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spelling	oai:doaj.org-article:be5a242b58dd4f45b8ccc803ecf5b2ad2021-11-30T18:50:37ZDevelopment and Validation of a Prognostic N6-Methyladenosine-Related Immune Gene Signature for Lung Adenocarcinoma1178-7066https://doaj.org/article/be5a242b58dd4f45b8ccc803ecf5b2ad2021-11-01T00:00:00Zhttps://www.dovepress.com/development-and-validation-of-a-prognostic-n6-methyladenosine-related--peer-reviewed-fulltext-article-PGPMhttps://doaj.org/toc/1178-7066Lemeng Zhang, Yongzhong Luo, Tianli Cheng, Jianhua Chen, Hua Yang, Xiaoping Wen, Zhou Jiang, Haitao Li, Changqie Pan Thoracic Medicine Department 1, Hunan Cancer Hospital, Changsha, Hunan Province, 410013, People’s Republic of ChinaCorrespondence: Yongzhong Luo Tel/Fax +86-731-89762220Email luoyongzhong@hnca.org.cnPurpose: The prognostic value of an N6-methyladenosine (m6A) methylation-related immune gene signature for lung adenocarcinoma (LUAD) was investigated.Patients and Methods: Gene expression and clinical phenotype data of LUAD patients were downloaded from The Cancer Genome Atlas database. A list of immune-related genes was retrieved from the InnateDB database. Correlation analysis, survival analysis, and univariate and multivariate Cox regression analyses were performed. After allocating patients into a high-risk or a low-risk group, the corresponding survival rates, immune microenvironment, expression of immune checkpoint genes, and modulation of Kyoto Encyclopedia of Genes and Genomes pathways were examined. Finally, the expression levels of prognostic biomarkers were assessed in the GSE126044 dataset.Results: Seven m6A-related immune prognostic genes were identified. High expression of PSMD10P1, DIDO1, ABCA5, and CIITA was associated with high survival rates, while that of PRC1, ZWILCH, and ANLN was associated with low survival rates. The high- and low-risk groups showed significant differences in terms of the abundance of six tumor-infiltrating immune cell types and expression of 12 immune checkpoint genes. The risk group acted as an independent prognostic factor (hazard ratio = 0.398, 95% confidence interval = 0.217– 0.729, P = 0.003). Finally, the developed nomogram could predict most efficiently the 1-, 2-, and 3-year survival probability of LUAD patients with a C-index of 0.833.Conclusion: A seven-gene risk signature, associated with the immune microenvironment in LUAD, showed independent prognostic value.Keywords: lung adenocarcinoma, N6-methyladenosine methylation, immune-related genes, immune microenvironment, prognostic signatureZhang LLuo YCheng TChen JYang HWen XJiang ZLi HPan CDove Medical Pressarticlelung adenocarcinoman6-methyladenosine methylationimmune-related genesimmune microenvironmentprognostic signatureTherapeutics. PharmacologyRM1-950ENPharmacogenomics and Personalized Medicine, Vol Volume 14, Pp 1549-1563 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	lung adenocarcinoma n6-methyladenosine methylation immune-related genes immune microenvironment prognostic signature Therapeutics. Pharmacology RM1-950
spellingShingle	lung adenocarcinoma n6-methyladenosine methylation immune-related genes immune microenvironment prognostic signature Therapeutics. Pharmacology RM1-950 Zhang L Luo Y Cheng T Chen J Yang H Wen X Jiang Z Li H Pan C Development and Validation of a Prognostic N6-Methyladenosine-Related Immune Gene Signature for Lung Adenocarcinoma
description	Lemeng Zhang, Yongzhong Luo, Tianli Cheng, Jianhua Chen, Hua Yang, Xiaoping Wen, Zhou Jiang, Haitao Li, Changqie Pan Thoracic Medicine Department 1, Hunan Cancer Hospital, Changsha, Hunan Province, 410013, People’s Republic of ChinaCorrespondence: Yongzhong Luo Tel/Fax +86-731-89762220Email luoyongzhong@hnca.org.cnPurpose: The prognostic value of an N6-methyladenosine (m6A) methylation-related immune gene signature for lung adenocarcinoma (LUAD) was investigated.Patients and Methods: Gene expression and clinical phenotype data of LUAD patients were downloaded from The Cancer Genome Atlas database. A list of immune-related genes was retrieved from the InnateDB database. Correlation analysis, survival analysis, and univariate and multivariate Cox regression analyses were performed. After allocating patients into a high-risk or a low-risk group, the corresponding survival rates, immune microenvironment, expression of immune checkpoint genes, and modulation of Kyoto Encyclopedia of Genes and Genomes pathways were examined. Finally, the expression levels of prognostic biomarkers were assessed in the GSE126044 dataset.Results: Seven m6A-related immune prognostic genes were identified. High expression of PSMD10P1, DIDO1, ABCA5, and CIITA was associated with high survival rates, while that of PRC1, ZWILCH, and ANLN was associated with low survival rates. The high- and low-risk groups showed significant differences in terms of the abundance of six tumor-infiltrating immune cell types and expression of 12 immune checkpoint genes. The risk group acted as an independent prognostic factor (hazard ratio = 0.398, 95% confidence interval = 0.217– 0.729, P = 0.003). Finally, the developed nomogram could predict most efficiently the 1-, 2-, and 3-year survival probability of LUAD patients with a C-index of 0.833.Conclusion: A seven-gene risk signature, associated with the immune microenvironment in LUAD, showed independent prognostic value.Keywords: lung adenocarcinoma, N6-methyladenosine methylation, immune-related genes, immune microenvironment, prognostic signature
format	article
author	Zhang L Luo Y Cheng T Chen J Yang H Wen X Jiang Z Li H Pan C
author_facet	Zhang L Luo Y Cheng T Chen J Yang H Wen X Jiang Z Li H Pan C
author_sort	Zhang L
title	Development and Validation of a Prognostic N6-Methyladenosine-Related Immune Gene Signature for Lung Adenocarcinoma
title_short	Development and Validation of a Prognostic N6-Methyladenosine-Related Immune Gene Signature for Lung Adenocarcinoma
title_full	Development and Validation of a Prognostic N6-Methyladenosine-Related Immune Gene Signature for Lung Adenocarcinoma
title_fullStr	Development and Validation of a Prognostic N6-Methyladenosine-Related Immune Gene Signature for Lung Adenocarcinoma
title_full_unstemmed	Development and Validation of a Prognostic N6-Methyladenosine-Related Immune Gene Signature for Lung Adenocarcinoma
title_sort	development and validation of a prognostic n6-methyladenosine-related immune gene signature for lung adenocarcinoma
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/be5a242b58dd4f45b8ccc803ecf5b2ad
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Development and Validation of a Prognostic N6-Methyladenosine-Related Immune Gene Signature for Lung Adenocarcinoma

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