Exploration of prognostic biomarkers and therapeutic targets in the microenvironment of bladder cancer based on CXC chemokines

Background: Bladder cancer (BLCA) has a high rate of morbidity and mortality, and is considered as one of the most malignant tumors of the urinary system. Tumor cells interact with surrounding interstitial cells, playing a key role in carcinogenesis and progression, which is partly mediated by chem...

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Autores principales:	Xiaoqi Sun, Qunxi Chen, Lihong Zhang, Jiewei Chen, Xinke Zhang
Formato:	article
Lenguaje:	EN
Publicado:	AIMS Press 2021
Materias:	bladder cancer biomarkers cxc chemokines microenvironment Biotechnology TP248.13-248.65 Mathematics QA1-939
Acceso en línea:	https://doaj.org/article/df146824bebc430ca4a6737fe12b404d
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spelling	oai:doaj.org-article:df146824bebc430ca4a6737fe12b404d2021-11-11T01:17:44ZExploration of prognostic biomarkers and therapeutic targets in the microenvironment of bladder cancer based on CXC chemokines10.3934/mbe.20213131551-0018https://doaj.org/article/df146824bebc430ca4a6737fe12b404d2021-07-01T00:00:00Zhttps://www.aimspress.com/article/doi/10.3934/mbe.2021313?viewType=HTMLhttps://doaj.org/toc/1551-0018Background: Bladder cancer (BLCA) has a high rate of morbidity and mortality, and is considered as one of the most malignant tumors of the urinary system. Tumor cells interact with surrounding interstitial cells, playing a key role in carcinogenesis and progression, which is partly mediated by chemokines. CXC chemokines exert anti-tumor biological roles in the tumor microenvironment and affect patient prognosis. Nevertheless, their expression and prognostic values patients with BLCA remain unclear. Methods: We used online tools, including Oncomine, UALCAN, GEPIA, GEO databases, cBioPortal, GeneMANIA, DAVID 6.8, Metascape, TRUST (version 2.0), LinkedOmics, TCGA, and TIMER2.0 to perform the relevant analysis. Results: The mRNA levels of C-X-C motif chemokine ligand (CXCL)1, CXCL5, CXCL6, CXCL7, CXCL9, CXCL10, CXCL11, CXCL13, CXCL16, and CXCL17 were increased significantly increased, and those of CXCL2, CXCL3, and CXCL12 were decreased significantly in BLCA tissues as assessed using the Oncomine, TCGA, and GEO databases. GEO showed that high levels of CXCL1, CXCL6, CXCL10, CXCL11, and CXCL13 mRNA expression are associated significantly with the poor overall survival (all p < 0.05), and similarly, those of CXCL2 and CXCL12 in the TCGA database (p < 0.05). The predominant signaling pathways involving the differentially expressed CXC chemokines are cell cycle, chemokine, and cytokine-cytokine receptor interaction. Moreover, transcription factors such as Sp1 transcription factor (SP1), nuclear factor kappa B subunit 1 (NFKB1), and RELA proto-oncogene, NF-KB subunit (RELA) were likely play critical roles in regulating CXC chemokine expression. LYN proto-oncogene, src family tyrosine kinase (LYN) and LCK proto-oncogene, src family tyrosine kinase (LCK) were identified as the key targets of these CXC chemokines. MicroRNAs miR200 and miR30 were identified as the main microRNAs that interact with several CXC chemokines through an miRNA-target network. The expression of these chemokines is closely associated with the infiltration of six categories of immune cells. Conclusion: We explored the CXC chemokines superfamily-based biomarkers associated with BLCA prognosis using public databases, and provided possible chemokine targets for patients with BLCA.Xiaoqi Sun Qunxi ChenLihong Zhang Jiewei ChenXinke ZhangAIMS Pressarticlebladder cancerbiomarkerscxc chemokinesmicroenvironmentBiotechnologyTP248.13-248.65MathematicsQA1-939ENMathematical Biosciences and Engineering, Vol 18, Iss 5, Pp 6262-6287 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	bladder cancer biomarkers cxc chemokines microenvironment Biotechnology TP248.13-248.65 Mathematics QA1-939
spellingShingle	bladder cancer biomarkers cxc chemokines microenvironment Biotechnology TP248.13-248.65 Mathematics QA1-939 Xiaoqi Sun Qunxi Chen Lihong Zhang Jiewei Chen Xinke Zhang Exploration of prognostic biomarkers and therapeutic targets in the microenvironment of bladder cancer based on CXC chemokines
description	Background: Bladder cancer (BLCA) has a high rate of morbidity and mortality, and is considered as one of the most malignant tumors of the urinary system. Tumor cells interact with surrounding interstitial cells, playing a key role in carcinogenesis and progression, which is partly mediated by chemokines. CXC chemokines exert anti-tumor biological roles in the tumor microenvironment and affect patient prognosis. Nevertheless, their expression and prognostic values patients with BLCA remain unclear. Methods: We used online tools, including Oncomine, UALCAN, GEPIA, GEO databases, cBioPortal, GeneMANIA, DAVID 6.8, Metascape, TRUST (version 2.0), LinkedOmics, TCGA, and TIMER2.0 to perform the relevant analysis. Results: The mRNA levels of C-X-C motif chemokine ligand (CXCL)1, CXCL5, CXCL6, CXCL7, CXCL9, CXCL10, CXCL11, CXCL13, CXCL16, and CXCL17 were increased significantly increased, and those of CXCL2, CXCL3, and CXCL12 were decreased significantly in BLCA tissues as assessed using the Oncomine, TCGA, and GEO databases. GEO showed that high levels of CXCL1, CXCL6, CXCL10, CXCL11, and CXCL13 mRNA expression are associated significantly with the poor overall survival (all p < 0.05), and similarly, those of CXCL2 and CXCL12 in the TCGA database (p < 0.05). The predominant signaling pathways involving the differentially expressed CXC chemokines are cell cycle, chemokine, and cytokine-cytokine receptor interaction. Moreover, transcription factors such as Sp1 transcription factor (SP1), nuclear factor kappa B subunit 1 (NFKB1), and RELA proto-oncogene, NF-KB subunit (RELA) were likely play critical roles in regulating CXC chemokine expression. LYN proto-oncogene, src family tyrosine kinase (LYN) and LCK proto-oncogene, src family tyrosine kinase (LCK) were identified as the key targets of these CXC chemokines. MicroRNAs miR200 and miR30 were identified as the main microRNAs that interact with several CXC chemokines through an miRNA-target network. The expression of these chemokines is closely associated with the infiltration of six categories of immune cells. Conclusion: We explored the CXC chemokines superfamily-based biomarkers associated with BLCA prognosis using public databases, and provided possible chemokine targets for patients with BLCA.
format	article
author	Xiaoqi Sun Qunxi Chen Lihong Zhang Jiewei Chen Xinke Zhang
author_facet	Xiaoqi Sun Qunxi Chen Lihong Zhang Jiewei Chen Xinke Zhang
author_sort	Xiaoqi Sun
title	Exploration of prognostic biomarkers and therapeutic targets in the microenvironment of bladder cancer based on CXC chemokines
title_short	Exploration of prognostic biomarkers and therapeutic targets in the microenvironment of bladder cancer based on CXC chemokines
title_full	Exploration of prognostic biomarkers and therapeutic targets in the microenvironment of bladder cancer based on CXC chemokines
title_fullStr	Exploration of prognostic biomarkers and therapeutic targets in the microenvironment of bladder cancer based on CXC chemokines
title_full_unstemmed	Exploration of prognostic biomarkers and therapeutic targets in the microenvironment of bladder cancer based on CXC chemokines
title_sort	exploration of prognostic biomarkers and therapeutic targets in the microenvironment of bladder cancer based on cxc chemokines
publisher	AIMS Press
publishDate	2021
url	https://doaj.org/article/df146824bebc430ca4a6737fe12b404d
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Exploration of prognostic biomarkers and therapeutic targets in the microenvironment of bladder cancer based on CXC chemokines

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