Identification of Clinical and Tumor Microenvironment Characteristics of Hypoxia-Related Risk Signature in Lung Adenocarcinoma

Background: Lung cancer is the leading cause of cancer-related death globally. Hypoxia can suppress the activation of the tumor microenvironment (TME), which contributes to distant metastasis. However, the role of hypoxia-mediated TME in predicting the diagnosis and prognosis of lung adenocarcinoma...

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Autores principales:	Zili Dai, Taisheng Liu, Guihong Liu, Zhen Deng, Peng Yu, Baiyao Wang, Bohong Cen, Liyi Guo, Jian Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	lung cancer hypoxia immunity overall survival risk signature Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/114a8744e5144248b237874bfbd8e4ef
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spelling	oai:doaj.org-article:114a8744e5144248b237874bfbd8e4ef2021-11-15T06:59:12ZIdentification of Clinical and Tumor Microenvironment Characteristics of Hypoxia-Related Risk Signature in Lung Adenocarcinoma2296-889X10.3389/fmolb.2021.757421https://doaj.org/article/114a8744e5144248b237874bfbd8e4ef2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmolb.2021.757421/fullhttps://doaj.org/toc/2296-889XBackground: Lung cancer is the leading cause of cancer-related death globally. Hypoxia can suppress the activation of the tumor microenvironment (TME), which contributes to distant metastasis. However, the role of hypoxia-mediated TME in predicting the diagnosis and prognosis of lung adenocarcinoma (LUAD) patients remains unclear.Methods: Both RNA and clinical data from the LUAD cohort were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Both univariate and multivariate Cox regression analyses were used to further screen prognosis-related hypoxia gene clusters. Time-dependent receiver operation characteristic (ROC) curves were established to evaluate the predictive sensitivity and specificity of the hypoxia-related risk signature. The characterization of gene set enrichment analysis (GSEA) and TME immune cell infiltration were further explored to identify hypoxia-related immune infiltration.Results: Eight hypoxia-related genes (LDHA, DCN, PGK1, PFKP, FBP1, LOX, ENO3, and CXCR4) were identified and established to construct a hypoxia-related risk signature. The high-risk group showed a poor overall survival compared to that of the low-risk group in the TCGA and GSE68465 cohorts (p < 0.0001). The AUCs for 1-, 3-, and 5-year overall survival were 0.736 vs. 0.741, 0.656 vs. 0.737, and 0.628 vs. 0.649, respectively. The high-risk group was associated with immunosuppression in the TME.Conclusion: The hypoxia-related risk signature may represent an independent biomarker that can differentiate the characteristics of TME immune cell infiltration and predict the prognosis of LUAD.Zili DaiTaisheng LiuGuihong LiuZhen DengPeng YuBaiyao WangBohong CenLiyi GuoJian ZhangFrontiers Media S.A.articlelung cancerhypoxiaimmunityoverall survivalrisk signatureBiology (General)QH301-705.5ENFrontiers in Molecular Biosciences, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	lung cancer hypoxia immunity overall survival risk signature Biology (General) QH301-705.5
spellingShingle	lung cancer hypoxia immunity overall survival risk signature Biology (General) QH301-705.5 Zili Dai Taisheng Liu Guihong Liu Zhen Deng Peng Yu Baiyao Wang Bohong Cen Liyi Guo Jian Zhang Identification of Clinical and Tumor Microenvironment Characteristics of Hypoxia-Related Risk Signature in Lung Adenocarcinoma
description	Background: Lung cancer is the leading cause of cancer-related death globally. Hypoxia can suppress the activation of the tumor microenvironment (TME), which contributes to distant metastasis. However, the role of hypoxia-mediated TME in predicting the diagnosis and prognosis of lung adenocarcinoma (LUAD) patients remains unclear.Methods: Both RNA and clinical data from the LUAD cohort were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Both univariate and multivariate Cox regression analyses were used to further screen prognosis-related hypoxia gene clusters. Time-dependent receiver operation characteristic (ROC) curves were established to evaluate the predictive sensitivity and specificity of the hypoxia-related risk signature. The characterization of gene set enrichment analysis (GSEA) and TME immune cell infiltration were further explored to identify hypoxia-related immune infiltration.Results: Eight hypoxia-related genes (LDHA, DCN, PGK1, PFKP, FBP1, LOX, ENO3, and CXCR4) were identified and established to construct a hypoxia-related risk signature. The high-risk group showed a poor overall survival compared to that of the low-risk group in the TCGA and GSE68465 cohorts (p < 0.0001). The AUCs for 1-, 3-, and 5-year overall survival were 0.736 vs. 0.741, 0.656 vs. 0.737, and 0.628 vs. 0.649, respectively. The high-risk group was associated with immunosuppression in the TME.Conclusion: The hypoxia-related risk signature may represent an independent biomarker that can differentiate the characteristics of TME immune cell infiltration and predict the prognosis of LUAD.
format	article
author	Zili Dai Taisheng Liu Guihong Liu Zhen Deng Peng Yu Baiyao Wang Bohong Cen Liyi Guo Jian Zhang
author_facet	Zili Dai Taisheng Liu Guihong Liu Zhen Deng Peng Yu Baiyao Wang Bohong Cen Liyi Guo Jian Zhang
author_sort	Zili Dai
title	Identification of Clinical and Tumor Microenvironment Characteristics of Hypoxia-Related Risk Signature in Lung Adenocarcinoma
title_short	Identification of Clinical and Tumor Microenvironment Characteristics of Hypoxia-Related Risk Signature in Lung Adenocarcinoma
title_full	Identification of Clinical and Tumor Microenvironment Characteristics of Hypoxia-Related Risk Signature in Lung Adenocarcinoma
title_fullStr	Identification of Clinical and Tumor Microenvironment Characteristics of Hypoxia-Related Risk Signature in Lung Adenocarcinoma
title_full_unstemmed	Identification of Clinical and Tumor Microenvironment Characteristics of Hypoxia-Related Risk Signature in Lung Adenocarcinoma
title_sort	identification of clinical and tumor microenvironment characteristics of hypoxia-related risk signature in lung adenocarcinoma
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/114a8744e5144248b237874bfbd8e4ef
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Identification of Clinical and Tumor Microenvironment Characteristics of Hypoxia-Related Risk Signature in Lung Adenocarcinoma

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