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Prognostic impact of the combination of HIF‑1α and GLUT1 in patients with oesophageal squamous cell carcinoma
Oesophageal squamous cell carcinoma (ESCC) is a common type of carcinoma. Hypoxia is associated with chemo- and radio-resistance, which may lead to a poor prognosis. Hypoxia-inducible factor-1α (HIF-1α) is the main transcriptional regulator of the cellular response to low oxygen levels. Moreover, it...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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D.A. Spandidos
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10433721/ https://www.ncbi.nlm.nih.gov/pubmed/37600334 http://dx.doi.org/10.3892/ol.2023.13990 |
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author | Yi, Hanjie Han, Yongqin Li, Qin Lin, Runduan Zhang, Jia Yang, Yun Wang, Xueping Zhang, Lin |
author_facet | Yi, Hanjie Han, Yongqin Li, Qin Lin, Runduan Zhang, Jia Yang, Yun Wang, Xueping Zhang, Lin |
author_sort | Yi, Hanjie |
collection | PubMed |
description | Oesophageal squamous cell carcinoma (ESCC) is a common type of carcinoma. Hypoxia is associated with chemo- and radio-resistance, which may lead to a poor prognosis. Hypoxia-inducible factor-1α (HIF-1α) is the main transcriptional regulator of the cellular response to low oxygen levels. Moreover, it can trigger the expression of critical genes, including glucose transporter protein type 1 (GLUT1). The aim of the present study was to evaluate the roles of HIF-1α and GLUT1 in ESCC and their usefulness as prognostic markers. HIF-1α and GLUT1 were measured in four ESCC cell lines, namely Eca109, KYSE150, TE-1 and TE-10, by western blotting following culture under normoxic and hypoxic conditions. In addition, xenograft tumors were established in mice using normoxic and hypoxic Eca109 cells and the chemosensitivity of the xenografts to 5-fluorouracil (5-FU) was evaluated. Furthermore, HIF-1α and GLUT1 were analysed by immunochemistry in the tumor tissues of patients with ESCC and the associations of their expression levels with clinicopathological parameters were investigated. The results revealed that HIF-1α and GLUT1 protein expression was weak in all four cell lines under a normoxic atmosphere but increased following culture in a hypoxic environment. In vivo, 5-FU inhibited tumor growth more strongly in normoxic Eca109 ×enografts than hypoxic Eca109 ×enografts. Higher levels of apoptosis were also detected in the normoxic Eca109 ×enografts via western blotting and TUNEL analysis. In patients with ESCC, HIF-1α expression was associated with advanced ESCC while GLUT1 expression was associated with the sex of the patients. Multivariate analysis demonstrated that HIF-1α and GLUT1 were negatively associated with progression-free survival (PFS) and overall survival (OS). Additionally, a combination of HIF-1α and GLUT1 expression was a predictor of RFS and OS in patients with ESCC without lymph node metastasis but not those with lymph node metastasis. The study demonstrated that HIF-1α and GLUT1 were strongly expressed in vitro and in xenograft models when cells were exposed to hypoxia. The simultaneous high expression of HIF-1α and GLUT1 was associated with poorer survival, and may play an important role in ESCC chemoresistance and the prognosis of ESCC. |
format | Online Article Text |
id | pubmed-10433721 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-104337212023-08-18 Prognostic impact of the combination of HIF‑1α and GLUT1 in patients with oesophageal squamous cell carcinoma Yi, Hanjie Han, Yongqin Li, Qin Lin, Runduan Zhang, Jia Yang, Yun Wang, Xueping Zhang, Lin Oncol Lett Articles Oesophageal squamous cell carcinoma (ESCC) is a common type of carcinoma. Hypoxia is associated with chemo- and radio-resistance, which may lead to a poor prognosis. Hypoxia-inducible factor-1α (HIF-1α) is the main transcriptional regulator of the cellular response to low oxygen levels. Moreover, it can trigger the expression of critical genes, including glucose transporter protein type 1 (GLUT1). The aim of the present study was to evaluate the roles of HIF-1α and GLUT1 in ESCC and their usefulness as prognostic markers. HIF-1α and GLUT1 were measured in four ESCC cell lines, namely Eca109, KYSE150, TE-1 and TE-10, by western blotting following culture under normoxic and hypoxic conditions. In addition, xenograft tumors were established in mice using normoxic and hypoxic Eca109 cells and the chemosensitivity of the xenografts to 5-fluorouracil (5-FU) was evaluated. Furthermore, HIF-1α and GLUT1 were analysed by immunochemistry in the tumor tissues of patients with ESCC and the associations of their expression levels with clinicopathological parameters were investigated. The results revealed that HIF-1α and GLUT1 protein expression was weak in all four cell lines under a normoxic atmosphere but increased following culture in a hypoxic environment. In vivo, 5-FU inhibited tumor growth more strongly in normoxic Eca109 ×enografts than hypoxic Eca109 ×enografts. Higher levels of apoptosis were also detected in the normoxic Eca109 ×enografts via western blotting and TUNEL analysis. In patients with ESCC, HIF-1α expression was associated with advanced ESCC while GLUT1 expression was associated with the sex of the patients. Multivariate analysis demonstrated that HIF-1α and GLUT1 were negatively associated with progression-free survival (PFS) and overall survival (OS). Additionally, a combination of HIF-1α and GLUT1 expression was a predictor of RFS and OS in patients with ESCC without lymph node metastasis but not those with lymph node metastasis. The study demonstrated that HIF-1α and GLUT1 were strongly expressed in vitro and in xenograft models when cells were exposed to hypoxia. The simultaneous high expression of HIF-1α and GLUT1 was associated with poorer survival, and may play an important role in ESCC chemoresistance and the prognosis of ESCC. D.A. Spandidos 2023-07-31 /pmc/articles/PMC10433721/ /pubmed/37600334 http://dx.doi.org/10.3892/ol.2023.13990 Text en Copyright: © Yi et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Yi, Hanjie Han, Yongqin Li, Qin Lin, Runduan Zhang, Jia Yang, Yun Wang, Xueping Zhang, Lin Prognostic impact of the combination of HIF‑1α and GLUT1 in patients with oesophageal squamous cell carcinoma |
title | Prognostic impact of the combination of HIF‑1α and GLUT1 in patients with oesophageal squamous cell carcinoma |
title_full | Prognostic impact of the combination of HIF‑1α and GLUT1 in patients with oesophageal squamous cell carcinoma |
title_fullStr | Prognostic impact of the combination of HIF‑1α and GLUT1 in patients with oesophageal squamous cell carcinoma |
title_full_unstemmed | Prognostic impact of the combination of HIF‑1α and GLUT1 in patients with oesophageal squamous cell carcinoma |
title_short | Prognostic impact of the combination of HIF‑1α and GLUT1 in patients with oesophageal squamous cell carcinoma |
title_sort | prognostic impact of the combination of hif‑1α and glut1 in patients with oesophageal squamous cell carcinoma |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10433721/ https://www.ncbi.nlm.nih.gov/pubmed/37600334 http://dx.doi.org/10.3892/ol.2023.13990 |
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