Identification of a Hypoxia-Associated Signature for Lung Adenocarcinoma

BackgroundA hypoxia microenvironment plays a role in the initiation and progression of many cancer types, but its involvement in lung adenocarcinoma is still unclear. This study aimed to explore the potential correlation between hypoxia and lung adenocarcinoma and establish the hypoxia-associated ge...

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Main Authors: Zhuomao Mo, Ling Yu, Zhirui Cao, Hao Hu, Shaoju Luo, Shijun Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-06-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fgene.2020.00647/full
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spelling doaj-2dd8ad2ffd394245b39131862ec037202020-11-25T02:30:57ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-06-011110.3389/fgene.2020.00647524578Identification of a Hypoxia-Associated Signature for Lung AdenocarcinomaZhuomao MoLing YuZhirui CaoHao HuShaoju LuoShijun ZhangBackgroundA hypoxia microenvironment plays a role in the initiation and progression of many cancer types, but its involvement in lung adenocarcinoma is still unclear. This study aimed to explore the potential correlation between hypoxia and lung adenocarcinoma and establish the hypoxia-associated gene signature in lung adenocarcinoma.MethodsLung adenocarcinoma cases were retrieved from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The genes to be included in the hypoxia-associated signature were selected by performing univariate Cox regression analysis and lasso regression analysis. Then, the gene signature was verified by performing a survival analysis and constructing the multiple receiver operating characteristic (ROC) curve. The CIBERSORT tool was then used to investigate the potential correlation between the gene signature and immune cells. Moreover, a nomogram was constructed and evaluated by calculating the C-index.ResultsFour genes (XPNPEP1, ANGPTL4, SLC2A1, and PFKP) were included in the final signature. The results showed that patients in the high-risk group showed worse survival than those in the low-risk group. Moreover, we found two types of immune cells (memory activated CD4+ T cell and M0 macrophages) which showed a significant infiltration in the tissues of the high-risk group patients.ConclusionThe hypoxia-associated gene signature established and validated in this study could be used as a potential prognostic factor in lung adenocarcinoma and may guide the immunotherapy choice.https://www.frontiersin.org/article/10.3389/fgene.2020.00647/fulllung adenocarcinomahypoxiaprognostic factorsignatureTCGA
collection DOAJ
language English
format Article
sources DOAJ
author Zhuomao Mo
Ling Yu
Zhirui Cao
Hao Hu
Shaoju Luo
Shijun Zhang
spellingShingle Zhuomao Mo
Ling Yu
Zhirui Cao
Hao Hu
Shaoju Luo
Shijun Zhang
Identification of a Hypoxia-Associated Signature for Lung Adenocarcinoma
Frontiers in Genetics
lung adenocarcinoma
hypoxia
prognostic factor
signature
TCGA
author_facet Zhuomao Mo
Ling Yu
Zhirui Cao
Hao Hu
Shaoju Luo
Shijun Zhang
author_sort Zhuomao Mo
title Identification of a Hypoxia-Associated Signature for Lung Adenocarcinoma
title_short Identification of a Hypoxia-Associated Signature for Lung Adenocarcinoma
title_full Identification of a Hypoxia-Associated Signature for Lung Adenocarcinoma
title_fullStr Identification of a Hypoxia-Associated Signature for Lung Adenocarcinoma
title_full_unstemmed Identification of a Hypoxia-Associated Signature for Lung Adenocarcinoma
title_sort identification of a hypoxia-associated signature for lung adenocarcinoma
publisher Frontiers Media S.A.
series Frontiers in Genetics
issn 1664-8021
publishDate 2020-06-01
description BackgroundA hypoxia microenvironment plays a role in the initiation and progression of many cancer types, but its involvement in lung adenocarcinoma is still unclear. This study aimed to explore the potential correlation between hypoxia and lung adenocarcinoma and establish the hypoxia-associated gene signature in lung adenocarcinoma.MethodsLung adenocarcinoma cases were retrieved from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The genes to be included in the hypoxia-associated signature were selected by performing univariate Cox regression analysis and lasso regression analysis. Then, the gene signature was verified by performing a survival analysis and constructing the multiple receiver operating characteristic (ROC) curve. The CIBERSORT tool was then used to investigate the potential correlation between the gene signature and immune cells. Moreover, a nomogram was constructed and evaluated by calculating the C-index.ResultsFour genes (XPNPEP1, ANGPTL4, SLC2A1, and PFKP) were included in the final signature. The results showed that patients in the high-risk group showed worse survival than those in the low-risk group. Moreover, we found two types of immune cells (memory activated CD4+ T cell and M0 macrophages) which showed a significant infiltration in the tissues of the high-risk group patients.ConclusionThe hypoxia-associated gene signature established and validated in this study could be used as a potential prognostic factor in lung adenocarcinoma and may guide the immunotherapy choice.
topic lung adenocarcinoma
hypoxia
prognostic factor
signature
TCGA
url https://www.frontiersin.org/article/10.3389/fgene.2020.00647/full
work_keys_str_mv AT zhuomaomo identificationofahypoxiaassociatedsignatureforlungadenocarcinoma
AT lingyu identificationofahypoxiaassociatedsignatureforlungadenocarcinoma
AT zhiruicao identificationofahypoxiaassociatedsignatureforlungadenocarcinoma
AT haohu identificationofahypoxiaassociatedsignatureforlungadenocarcinoma
AT shaojuluo identificationofahypoxiaassociatedsignatureforlungadenocarcinoma
AT shijunzhang identificationofahypoxiaassociatedsignatureforlungadenocarcinoma
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