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Expression of hypoxia‐inducible factor 1α, glucose transporter 1, and hexokinase 2 in primary central nervous system lymphoma and the correlation with the biological behaviors

BACKGROUND: It has been indicated that abnormal glucose metabolism mediated by hypoxia‐inducible factor 1α (HIF‐1α) played an essential role in the development of solid tumor. However, there were rare studies about the role of them in primary central nervous system lymphoma (PCNSL). OBJECTIVE: To in...

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Autores principales: Shen, Na, Wang, Yaming, Sun, Xuefei, Bai, Xueyan, He, Jinglan, Cui, Qu, Qian, Jun, Zhu, Hong, Chen, Yuedan, Xing, Ruixian, Liu, Qing, Wu, Yuchen, Li, Junhong, Lai, Wenyuan, Sun, Shengjun, Ji, Nan, Liu, Yuanbo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428508/
https://www.ncbi.nlm.nih.gov/pubmed/32533646
http://dx.doi.org/10.1002/brb3.1718
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author Shen, Na
Wang, Yaming
Sun, Xuefei
Bai, Xueyan
He, Jinglan
Cui, Qu
Qian, Jun
Zhu, Hong
Chen, Yuedan
Xing, Ruixian
Liu, Qing
Wu, Yuchen
Li, Junhong
Lai, Wenyuan
Sun, Shengjun
Ji, Nan
Liu, Yuanbo
author_facet Shen, Na
Wang, Yaming
Sun, Xuefei
Bai, Xueyan
He, Jinglan
Cui, Qu
Qian, Jun
Zhu, Hong
Chen, Yuedan
Xing, Ruixian
Liu, Qing
Wu, Yuchen
Li, Junhong
Lai, Wenyuan
Sun, Shengjun
Ji, Nan
Liu, Yuanbo
author_sort Shen, Na
collection PubMed
description BACKGROUND: It has been indicated that abnormal glucose metabolism mediated by hypoxia‐inducible factor 1α (HIF‐1α) played an essential role in the development of solid tumor. However, there were rare studies about the role of them in primary central nervous system lymphoma (PCNSL). OBJECTIVE: To investigate the protein levels of HIF‐1α, glucose transporter 1 (GLUT1), and hexokinase 2 (HK2) in PCNSL and whether their levels are associated with prognostic factors. METHODS: Expression of HIF‐1α, GLUT1, and HK2 in 39 tumor tissues was evaluated by immunohistochemical stainning. The correlation of the expression of HIF‐1α with the protein level of GLUT1 and HK2 was investigated. In addition, the association between these protein expression levels and clinical parameters and prognosis was analyzed. RESULTS: In the tumor specimens of PCNSL, positive stainings of HIF‐1α, GLUT1, and HK2 were in 23 patients (58.97%), 25 patients (64.1%), and 26 patients (66.67%), respectively, which were associated with the expression level of lactic dehydrogenase (LDH), but not with age, gender, number of lesion, ECOG score, or deep structure. The expression of HIF‐1α was positively correlated with the expression of GLUT1 (p < .01, r = .749) and HK2 (p < .01, r = .787). Univariate analysis showed that upregulated GLUT1 was unfavorable predictors of progression‐free survival (PFS) in PCNSL. The results of Cox proportional hazards model showed GLUT1 was significantly associated with shorter PFS (hazard ration: 5.65; 95% confidence interval: 1.23–25.84; p = .026). CONCLUSIONS: This study indicated that there was a hypoxic microenvironment and HIF‐1α was involved in the regulation of glycolysis pathway in PCNSL. GLUT1 might be a potential marker for shorter PFS in PCNSL.
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spelling pubmed-74285082020-08-17 Expression of hypoxia‐inducible factor 1α, glucose transporter 1, and hexokinase 2 in primary central nervous system lymphoma and the correlation with the biological behaviors Shen, Na Wang, Yaming Sun, Xuefei Bai, Xueyan He, Jinglan Cui, Qu Qian, Jun Zhu, Hong Chen, Yuedan Xing, Ruixian Liu, Qing Wu, Yuchen Li, Junhong Lai, Wenyuan Sun, Shengjun Ji, Nan Liu, Yuanbo Brain Behav Original Research BACKGROUND: It has been indicated that abnormal glucose metabolism mediated by hypoxia‐inducible factor 1α (HIF‐1α) played an essential role in the development of solid tumor. However, there were rare studies about the role of them in primary central nervous system lymphoma (PCNSL). OBJECTIVE: To investigate the protein levels of HIF‐1α, glucose transporter 1 (GLUT1), and hexokinase 2 (HK2) in PCNSL and whether their levels are associated with prognostic factors. METHODS: Expression of HIF‐1α, GLUT1, and HK2 in 39 tumor tissues was evaluated by immunohistochemical stainning. The correlation of the expression of HIF‐1α with the protein level of GLUT1 and HK2 was investigated. In addition, the association between these protein expression levels and clinical parameters and prognosis was analyzed. RESULTS: In the tumor specimens of PCNSL, positive stainings of HIF‐1α, GLUT1, and HK2 were in 23 patients (58.97%), 25 patients (64.1%), and 26 patients (66.67%), respectively, which were associated with the expression level of lactic dehydrogenase (LDH), but not with age, gender, number of lesion, ECOG score, or deep structure. The expression of HIF‐1α was positively correlated with the expression of GLUT1 (p < .01, r = .749) and HK2 (p < .01, r = .787). Univariate analysis showed that upregulated GLUT1 was unfavorable predictors of progression‐free survival (PFS) in PCNSL. The results of Cox proportional hazards model showed GLUT1 was significantly associated with shorter PFS (hazard ration: 5.65; 95% confidence interval: 1.23–25.84; p = .026). CONCLUSIONS: This study indicated that there was a hypoxic microenvironment and HIF‐1α was involved in the regulation of glycolysis pathway in PCNSL. GLUT1 might be a potential marker for shorter PFS in PCNSL. John Wiley and Sons Inc. 2020-06-12 /pmc/articles/PMC7428508/ /pubmed/32533646 http://dx.doi.org/10.1002/brb3.1718 Text en © 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Shen, Na
Wang, Yaming
Sun, Xuefei
Bai, Xueyan
He, Jinglan
Cui, Qu
Qian, Jun
Zhu, Hong
Chen, Yuedan
Xing, Ruixian
Liu, Qing
Wu, Yuchen
Li, Junhong
Lai, Wenyuan
Sun, Shengjun
Ji, Nan
Liu, Yuanbo
Expression of hypoxia‐inducible factor 1α, glucose transporter 1, and hexokinase 2 in primary central nervous system lymphoma and the correlation with the biological behaviors
title Expression of hypoxia‐inducible factor 1α, glucose transporter 1, and hexokinase 2 in primary central nervous system lymphoma and the correlation with the biological behaviors
title_full Expression of hypoxia‐inducible factor 1α, glucose transporter 1, and hexokinase 2 in primary central nervous system lymphoma and the correlation with the biological behaviors
title_fullStr Expression of hypoxia‐inducible factor 1α, glucose transporter 1, and hexokinase 2 in primary central nervous system lymphoma and the correlation with the biological behaviors
title_full_unstemmed Expression of hypoxia‐inducible factor 1α, glucose transporter 1, and hexokinase 2 in primary central nervous system lymphoma and the correlation with the biological behaviors
title_short Expression of hypoxia‐inducible factor 1α, glucose transporter 1, and hexokinase 2 in primary central nervous system lymphoma and the correlation with the biological behaviors
title_sort expression of hypoxia‐inducible factor 1α, glucose transporter 1, and hexokinase 2 in primary central nervous system lymphoma and the correlation with the biological behaviors
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428508/
https://www.ncbi.nlm.nih.gov/pubmed/32533646
http://dx.doi.org/10.1002/brb3.1718
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