Neutrophils correlate with hypoxia microenvironment and promote progression of non-small-cell lung cancer

Hypoxia, a strong and selective pressure, has been involved in invasion, metastasis, and angiogenesis of tumor cells. Our study performed the transcriptome profiles of 666 non-small-cell lung cancer (NSCLC) patients. Various bioinformatic approaches were combined to evaluate the immune cell infiltra...

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Autores principales:	Chunyan Zhang, Bingxiang Tang, Jianping Hu, Xiang Fang, Hongzhi Bian, Junlei Han, Congxia Hou, Fang Sun
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	non-small-cell lung cancer hypoxia progression gene signature tumor-associated neutrophils cxcl6 Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/91022e6d937542eba71960f722ea1b1b
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spelling	oai:doaj.org-article:91022e6d937542eba71960f722ea1b1b2021-11-04T15:51:53ZNeutrophils correlate with hypoxia microenvironment and promote progression of non-small-cell lung cancer2165-59792165-598710.1080/21655979.2021.1987820https://doaj.org/article/91022e6d937542eba71960f722ea1b1b2021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.1987820https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Hypoxia, a strong and selective pressure, has been involved in invasion, metastasis, and angiogenesis of tumor cells. Our study performed the transcriptome profiles of 666 non-small-cell lung cancer (NSCLC) patients. Various bioinformatic approaches were combined to evaluate the immune cell infiltration in the high hypoxia risk patients. In addition, in vitro experiments were performed to assess the effects of tumor-associated neutrophils (TANs) on NSCLC cells proliferation, migration and invasion and to reveal the underlying mechanisms. We divided NSCLC into two groups (Cluster1/2) based on the expression profiles of hypoxia-associated genes. Compared with the Cluster1 subgroup, the Cluster2 had a worse prognosis. Significant enrichment analysis revealed that PI3K/AKT/mTOR signaling pathway and TANs were highly related to hypoxia microenvironment. Eleven hypoxia-related genes (FBP1, NDST2, ADM, LDHA, DDIT4, EXT1, BCAN, IGFBP1, PDGFB, AKAP12, and CDKN3) were scored by LASSO COX regression to yield risk scores, and we revealed a significant difference in overall survival (OS) between the low- and high-risk groups. Mechanistically, CXCL6 in hypoxic cancer cells promoted the migration of TANs in vitro, and in turn promote NSCLC cells proliferation, migration and invasion. In summary, this study revealed a 11‐hypoxia gene signature that predicted OS of NSCLC patients, and improved our understanding of the role of TANs in hypoxia microenvironment.Chunyan ZhangBingxiang TangJianping HuXiang FangHongzhi BianJunlei HanCongxia HouFang SunTaylor & Francis Grouparticlenon-small-cell lung cancerhypoxiaprogressiongene signaturetumor-associated neutrophilscxcl6BiotechnologyTP248.13-248.65ENBioengineered, Vol 12, Iss 1, Pp 8872-8884 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	non-small-cell lung cancer hypoxia progression gene signature tumor-associated neutrophils cxcl6 Biotechnology TP248.13-248.65
spellingShingle	non-small-cell lung cancer hypoxia progression gene signature tumor-associated neutrophils cxcl6 Biotechnology TP248.13-248.65 Chunyan Zhang Bingxiang Tang Jianping Hu Xiang Fang Hongzhi Bian Junlei Han Congxia Hou Fang Sun Neutrophils correlate with hypoxia microenvironment and promote progression of non-small-cell lung cancer
description	Hypoxia, a strong and selective pressure, has been involved in invasion, metastasis, and angiogenesis of tumor cells. Our study performed the transcriptome profiles of 666 non-small-cell lung cancer (NSCLC) patients. Various bioinformatic approaches were combined to evaluate the immune cell infiltration in the high hypoxia risk patients. In addition, in vitro experiments were performed to assess the effects of tumor-associated neutrophils (TANs) on NSCLC cells proliferation, migration and invasion and to reveal the underlying mechanisms. We divided NSCLC into two groups (Cluster1/2) based on the expression profiles of hypoxia-associated genes. Compared with the Cluster1 subgroup, the Cluster2 had a worse prognosis. Significant enrichment analysis revealed that PI3K/AKT/mTOR signaling pathway and TANs were highly related to hypoxia microenvironment. Eleven hypoxia-related genes (FBP1, NDST2, ADM, LDHA, DDIT4, EXT1, BCAN, IGFBP1, PDGFB, AKAP12, and CDKN3) were scored by LASSO COX regression to yield risk scores, and we revealed a significant difference in overall survival (OS) between the low- and high-risk groups. Mechanistically, CXCL6 in hypoxic cancer cells promoted the migration of TANs in vitro, and in turn promote NSCLC cells proliferation, migration and invasion. In summary, this study revealed a 11‐hypoxia gene signature that predicted OS of NSCLC patients, and improved our understanding of the role of TANs in hypoxia microenvironment.
format	article
author	Chunyan Zhang Bingxiang Tang Jianping Hu Xiang Fang Hongzhi Bian Junlei Han Congxia Hou Fang Sun
author_facet	Chunyan Zhang Bingxiang Tang Jianping Hu Xiang Fang Hongzhi Bian Junlei Han Congxia Hou Fang Sun
author_sort	Chunyan Zhang
title	Neutrophils correlate with hypoxia microenvironment and promote progression of non-small-cell lung cancer
title_short	Neutrophils correlate with hypoxia microenvironment and promote progression of non-small-cell lung cancer
title_full	Neutrophils correlate with hypoxia microenvironment and promote progression of non-small-cell lung cancer
title_fullStr	Neutrophils correlate with hypoxia microenvironment and promote progression of non-small-cell lung cancer
title_full_unstemmed	Neutrophils correlate with hypoxia microenvironment and promote progression of non-small-cell lung cancer
title_sort	neutrophils correlate with hypoxia microenvironment and promote progression of non-small-cell lung cancer
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/91022e6d937542eba71960f722ea1b1b
work_keys_str_mv	AT chunyanzhang neutrophilscorrelatewithhypoxiamicroenvironmentandpromoteprogressionofnonsmallcelllungcancer AT bingxiangtang neutrophilscorrelatewithhypoxiamicroenvironmentandpromoteprogressionofnonsmallcelllungcancer AT jianpinghu neutrophilscorrelatewithhypoxiamicroenvironmentandpromoteprogressionofnonsmallcelllungcancer AT xiangfang neutrophilscorrelatewithhypoxiamicroenvironmentandpromoteprogressionofnonsmallcelllungcancer AT hongzhibian neutrophilscorrelatewithhypoxiamicroenvironmentandpromoteprogressionofnonsmallcelllungcancer AT junleihan neutrophilscorrelatewithhypoxiamicroenvironmentandpromoteprogressionofnonsmallcelllungcancer AT congxiahou neutrophilscorrelatewithhypoxiamicroenvironmentandpromoteprogressionofnonsmallcelllungcancer AT fangsun neutrophilscorrelatewithhypoxiamicroenvironmentandpromoteprogressionofnonsmallcelllungcancer
_version_	1718444727977639936

Neutrophils correlate with hypoxia microenvironment and promote progression of non-small-cell lung cancer

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