Integrated bioinformatics analysis of differentially expressed genes and immune cell infiltration characteristics in Esophageal Squamous cell carcinoma

Abstract Esophageal squamous cell carcinoma (ESCC) is a life-threatening thoracic tumor with a poor prognosis. The role of molecular alterations and the immune microenvironment in ESCC development has not been fully elucidated. The present study aimed to elucidate key candidate genes and immune cell...

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Autores principales: Zitong Feng, Jingge Qu, Xiao Liu, Jinghui Liang, Yongmeng Li, Jin Jiang, Huiying Zhang, Hui Tian
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/c76b10a381ce416aa305676683c7222c
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spelling oai:doaj.org-article:c76b10a381ce416aa305676683c7222c2021-12-02T17:08:43ZIntegrated bioinformatics analysis of differentially expressed genes and immune cell infiltration characteristics in Esophageal Squamous cell carcinoma10.1038/s41598-021-96274-y2045-2322https://doaj.org/article/c76b10a381ce416aa305676683c7222c2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96274-yhttps://doaj.org/toc/2045-2322Abstract Esophageal squamous cell carcinoma (ESCC) is a life-threatening thoracic tumor with a poor prognosis. The role of molecular alterations and the immune microenvironment in ESCC development has not been fully elucidated. The present study aimed to elucidate key candidate genes and immune cell infiltration characteristics in ESCC by integrated bioinformatics analysis. Nine gene expression datasets from the Gene Expression Omnibus (GEO) database were analysed to identify robust differentially expressed genes (DEGs) using the robust rank aggregation (RRA) algorithm. Functional enrichment analyses showed that the 152 robust DEGs are involved in multiple processes in the tumor microenvironment (TME). Immune cell infiltration analysis based on the 9 normalized GEO microarray datasets was conducted with the CIBERSORT algorithm. The changes in macrophages between ESCC and normal tissues were particularly obvious. In ESCC tissues, M0 and M1 macrophages were increased dramatically, while M2 macrophages were decreased. A robust DEG-based protein–protein interaction (PPI) network was used for hub gene selection with the CytoHubba plugin in Cytoscape. Nine hub genes (CDA, CXCL1, IGFBP3, MMP3, MMP11, PLAU, SERPINE1, SPP1 and VCAN) had high diagnostic efficiency for ESCC according to receiver operating characteristic (ROC) curve analysis. The expression of all hub genes except MMP3 and PLAU was significantly related to macrophage infiltration. Univariate and multivariate regression analyses showed that a 7-gene signature constructed from the robust DEGs was useful for predicting ESCC prognosis. Our results might facilitate the exploration of potential targeted TME therapies and prognostic evaluation in ESCC.Zitong FengJingge QuXiao LiuJinghui LiangYongmeng LiJin JiangHuiying ZhangHui TianNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Zitong Feng
Jingge Qu
Xiao Liu
Jinghui Liang
Yongmeng Li
Jin Jiang
Huiying Zhang
Hui Tian
Integrated bioinformatics analysis of differentially expressed genes and immune cell infiltration characteristics in Esophageal Squamous cell carcinoma
description Abstract Esophageal squamous cell carcinoma (ESCC) is a life-threatening thoracic tumor with a poor prognosis. The role of molecular alterations and the immune microenvironment in ESCC development has not been fully elucidated. The present study aimed to elucidate key candidate genes and immune cell infiltration characteristics in ESCC by integrated bioinformatics analysis. Nine gene expression datasets from the Gene Expression Omnibus (GEO) database were analysed to identify robust differentially expressed genes (DEGs) using the robust rank aggregation (RRA) algorithm. Functional enrichment analyses showed that the 152 robust DEGs are involved in multiple processes in the tumor microenvironment (TME). Immune cell infiltration analysis based on the 9 normalized GEO microarray datasets was conducted with the CIBERSORT algorithm. The changes in macrophages between ESCC and normal tissues were particularly obvious. In ESCC tissues, M0 and M1 macrophages were increased dramatically, while M2 macrophages were decreased. A robust DEG-based protein–protein interaction (PPI) network was used for hub gene selection with the CytoHubba plugin in Cytoscape. Nine hub genes (CDA, CXCL1, IGFBP3, MMP3, MMP11, PLAU, SERPINE1, SPP1 and VCAN) had high diagnostic efficiency for ESCC according to receiver operating characteristic (ROC) curve analysis. The expression of all hub genes except MMP3 and PLAU was significantly related to macrophage infiltration. Univariate and multivariate regression analyses showed that a 7-gene signature constructed from the robust DEGs was useful for predicting ESCC prognosis. Our results might facilitate the exploration of potential targeted TME therapies and prognostic evaluation in ESCC.
format article
author Zitong Feng
Jingge Qu
Xiao Liu
Jinghui Liang
Yongmeng Li
Jin Jiang
Huiying Zhang
Hui Tian
author_facet Zitong Feng
Jingge Qu
Xiao Liu
Jinghui Liang
Yongmeng Li
Jin Jiang
Huiying Zhang
Hui Tian
author_sort Zitong Feng
title Integrated bioinformatics analysis of differentially expressed genes and immune cell infiltration characteristics in Esophageal Squamous cell carcinoma
title_short Integrated bioinformatics analysis of differentially expressed genes and immune cell infiltration characteristics in Esophageal Squamous cell carcinoma
title_full Integrated bioinformatics analysis of differentially expressed genes and immune cell infiltration characteristics in Esophageal Squamous cell carcinoma
title_fullStr Integrated bioinformatics analysis of differentially expressed genes and immune cell infiltration characteristics in Esophageal Squamous cell carcinoma
title_full_unstemmed Integrated bioinformatics analysis of differentially expressed genes and immune cell infiltration characteristics in Esophageal Squamous cell carcinoma
title_sort integrated bioinformatics analysis of differentially expressed genes and immune cell infiltration characteristics in esophageal squamous cell carcinoma
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/c76b10a381ce416aa305676683c7222c
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