CC Chemokine Receptors in Lung Adenocarcinoma: The Inflammation-Related Prognostic Biomarkers and Immunotherapeutic Targets

Fangteng Liu,1,2 Hengyu Wu1 1Department of Breast Surgery, The Third Hospital of Nanchang, Nanchang, Jiangxi, 330009, People’s Republic of China; 2Faculty of Medicine, University of Munich, Munich, 80336, GermanyCorrespondence: Hengyu Wu Tel +86-15270280590Email why_wuhengyu0590@163.comBac...

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Autores principales:	Liu F, Wu H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	cc chemokine receptors lung adenocarcinoma prognostic biomarker immunotherapeutic target bioinformatics analysis Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/5cbe4caa40b4434e8b35224def77496d
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spelling	oai:doaj.org-article:5cbe4caa40b4434e8b35224def77496d2021-12-02T12:14:54ZCC Chemokine Receptors in Lung Adenocarcinoma: The Inflammation-Related Prognostic Biomarkers and Immunotherapeutic Targets1178-7031https://doaj.org/article/5cbe4caa40b4434e8b35224def77496d2021-02-01T00:00:00Zhttps://www.dovepress.com/cc-chemokine-receptors-in-lung-adenocarcinoma-the-inflammation-related-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Fangteng Liu,1,2 Hengyu Wu1 1Department of Breast Surgery, The Third Hospital of Nanchang, Nanchang, Jiangxi, 330009, People’s Republic of China; 2Faculty of Medicine, University of Munich, Munich, 80336, GermanyCorrespondence: Hengyu Wu Tel +86-15270280590Email why_wuhengyu0590@163.comBackground: Lung adenocarcinoma (LUAD) is the most common type of lung cancer with a high incidence and increased mortality. CC chemokine receptors were participating in the modulation of the tumor microenvironment and involved in carcinogenesis and tumor development. However, the potential mechanistic values of CC chemokine receptors as clinical biomarkers and therapeutic targets in LUAD have not been fully clarified.Methodology: ONCOMINE, UALCAN, GEPIA, Kaplan–Meier Plotter, SurvExpress, MethSurv, SurvivalMeth, cBioPortal, String, GeneMANIA, DAVID, Metascape, TRRUST, LinkedOmics, and Timer were applied in this work.Results: The transcriptional levels of CCR1/10 in LUAD tissues were significantly reduced while the transcriptional levels of CCR3/6/7/8 were significantly elevated, and the expression of CCR1 was the highest in LUAD among these CC chemokine receptors. A significant correlation was found between the expression of CCR2/4/6/7 and the pathological stage of LUAD patients. There were significant associations between CCR2/3/4/5/6/10 expression levels and OS in LUAD, and LUAD patients with high transcriptional levels of CCR3/4 had inferior first-progression survival. In addition, the prognostic values of CC chemokine receptors signature in LUAD were explored in three independent cohorts, the high-risk group displayed unfavorable OS compared with the low-risk group, and the LUAD cases in the high-risk group also suffered inferior RFS than that in the low-risk group. And for the prognostic value of the DNA methylation of CC chemokine receptors, we found 1 CpG of CCR2, 2 CpGs of CCR3, 1 CpG of CCR4, 3 CpGs of CCR6, 3 CpGs of CCR7, 1 CpG of CCR8, and 3 CpGs of CCR9 were significantly associated with prognosis in LUAD patients. However, the DNA methylation signature analysis showed there was no statistically significant association between the high- and low-risk group. For potential mechanism, the neighbor gene networks, interaction analyses, functional enrichment analyses of CC chemokine receptors in LUAD were performed, the transcription factor targets, kinase targets, and miRNA targets of CC chemokine receptors were also identified in LUAD. We also found significant correlations among CC chemokine receptors expression and the infiltration of immune cells, the tumor infiltration levels among LUAD with different somatic copy number alterations of these chemokine receptors were also assessed. Moreover, the Cox proportional hazard model showed that CCR1/2/10, B_cell, CD4_Tcell were significantly related to the clinical outcome of LUAD patients.Conclusion: CC chemokine receptors might serve as immunotherapeutic targets and prognostic biomarkers in LUAD.Keywords: CC chemokine receptors, lung adenocarcinoma, prognostic biomarker, immunotherapeutic target, bioinformatics analysisLiu FWu HDove Medical Pressarticlecc chemokine receptorslung adenocarcinomaprognostic biomarkerimmunotherapeutic targetbioinformatics analysisPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 267-285 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cc chemokine receptors lung adenocarcinoma prognostic biomarker immunotherapeutic target bioinformatics analysis Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	cc chemokine receptors lung adenocarcinoma prognostic biomarker immunotherapeutic target bioinformatics analysis Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Liu F Wu H CC Chemokine Receptors in Lung Adenocarcinoma: The Inflammation-Related Prognostic Biomarkers and Immunotherapeutic Targets
description	Fangteng Liu,1,2 Hengyu Wu1 1Department of Breast Surgery, The Third Hospital of Nanchang, Nanchang, Jiangxi, 330009, People’s Republic of China; 2Faculty of Medicine, University of Munich, Munich, 80336, GermanyCorrespondence: Hengyu Wu Tel +86-15270280590Email why_wuhengyu0590@163.comBackground: Lung adenocarcinoma (LUAD) is the most common type of lung cancer with a high incidence and increased mortality. CC chemokine receptors were participating in the modulation of the tumor microenvironment and involved in carcinogenesis and tumor development. However, the potential mechanistic values of CC chemokine receptors as clinical biomarkers and therapeutic targets in LUAD have not been fully clarified.Methodology: ONCOMINE, UALCAN, GEPIA, Kaplan–Meier Plotter, SurvExpress, MethSurv, SurvivalMeth, cBioPortal, String, GeneMANIA, DAVID, Metascape, TRRUST, LinkedOmics, and Timer were applied in this work.Results: The transcriptional levels of CCR1/10 in LUAD tissues were significantly reduced while the transcriptional levels of CCR3/6/7/8 were significantly elevated, and the expression of CCR1 was the highest in LUAD among these CC chemokine receptors. A significant correlation was found between the expression of CCR2/4/6/7 and the pathological stage of LUAD patients. There were significant associations between CCR2/3/4/5/6/10 expression levels and OS in LUAD, and LUAD patients with high transcriptional levels of CCR3/4 had inferior first-progression survival. In addition, the prognostic values of CC chemokine receptors signature in LUAD were explored in three independent cohorts, the high-risk group displayed unfavorable OS compared with the low-risk group, and the LUAD cases in the high-risk group also suffered inferior RFS than that in the low-risk group. And for the prognostic value of the DNA methylation of CC chemokine receptors, we found 1 CpG of CCR2, 2 CpGs of CCR3, 1 CpG of CCR4, 3 CpGs of CCR6, 3 CpGs of CCR7, 1 CpG of CCR8, and 3 CpGs of CCR9 were significantly associated with prognosis in LUAD patients. However, the DNA methylation signature analysis showed there was no statistically significant association between the high- and low-risk group. For potential mechanism, the neighbor gene networks, interaction analyses, functional enrichment analyses of CC chemokine receptors in LUAD were performed, the transcription factor targets, kinase targets, and miRNA targets of CC chemokine receptors were also identified in LUAD. We also found significant correlations among CC chemokine receptors expression and the infiltration of immune cells, the tumor infiltration levels among LUAD with different somatic copy number alterations of these chemokine receptors were also assessed. Moreover, the Cox proportional hazard model showed that CCR1/2/10, B_cell, CD4_Tcell were significantly related to the clinical outcome of LUAD patients.Conclusion: CC chemokine receptors might serve as immunotherapeutic targets and prognostic biomarkers in LUAD.Keywords: CC chemokine receptors, lung adenocarcinoma, prognostic biomarker, immunotherapeutic target, bioinformatics analysis
format	article
author	Liu F Wu H
author_facet	Liu F Wu H
author_sort	Liu F
title	CC Chemokine Receptors in Lung Adenocarcinoma: The Inflammation-Related Prognostic Biomarkers and Immunotherapeutic Targets
title_short	CC Chemokine Receptors in Lung Adenocarcinoma: The Inflammation-Related Prognostic Biomarkers and Immunotherapeutic Targets
title_full	CC Chemokine Receptors in Lung Adenocarcinoma: The Inflammation-Related Prognostic Biomarkers and Immunotherapeutic Targets
title_fullStr	CC Chemokine Receptors in Lung Adenocarcinoma: The Inflammation-Related Prognostic Biomarkers and Immunotherapeutic Targets
title_full_unstemmed	CC Chemokine Receptors in Lung Adenocarcinoma: The Inflammation-Related Prognostic Biomarkers and Immunotherapeutic Targets
title_sort	cc chemokine receptors in lung adenocarcinoma: the inflammation-related prognostic biomarkers and immunotherapeutic targets
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/5cbe4caa40b4434e8b35224def77496d
work_keys_str_mv	AT liuf ccchemokinereceptorsinlungadenocarcinomatheinflammationrelatedprognosticbiomarkersandimmunotherapeutictargets AT wuh ccchemokinereceptorsinlungadenocarcinomatheinflammationrelatedprognosticbiomarkersandimmunotherapeutictargets
_version_	1718394576137355264

CC Chemokine Receptors in Lung Adenocarcinoma: The Inflammation-Related Prognostic Biomarkers and Immunotherapeutic Targets

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