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High expression of hypoxia-inducible factor 1-alpha predicts poor prognosis in pancreatic ductal adenocarcinoma: a meta-analysis and database validation protocol

BACKGROUND: Hypoxia-inducible factor 1-alpha (HIF-1α) is overexpressed in pancreatic ductal adenocarcinomas (PDACs). However, the prognosis of high expression of HIF-1α in PDACs remains controversial because of lacking a solid support. A meta-analysis may help for a better understanding of the role...

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Autores principales: Zoa, Alexis, Yang, Yingjie, Huang, Wenjin, Yang, Jing, Wang, Jiangping, Wang, Haibo, Dong, Minghua, Tian, Yuantong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9552053/
https://www.ncbi.nlm.nih.gov/pubmed/36237265
http://dx.doi.org/10.21037/tcr-22-787
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author Zoa, Alexis
Yang, Yingjie
Huang, Wenjin
Yang, Jing
Wang, Jiangping
Wang, Haibo
Dong, Minghua
Tian, Yuantong
author_facet Zoa, Alexis
Yang, Yingjie
Huang, Wenjin
Yang, Jing
Wang, Jiangping
Wang, Haibo
Dong, Minghua
Tian, Yuantong
author_sort Zoa, Alexis
collection PubMed
description BACKGROUND: Hypoxia-inducible factor 1-alpha (HIF-1α) is overexpressed in pancreatic ductal adenocarcinomas (PDACs). However, the prognosis of high expression of HIF-1α in PDACs remains controversial because of lacking a solid support. A meta-analysis may help for a better understanding of the role of HIF-1α in the prognosis of PDACs. METHODS: By using a systematic approach, we conducted a meta-analysis from current literature. We performed an advanced search in PubMed, Embase, Cochrane Library and Web of Science databases. Recorded studies were published between September 1, 2001, and February 26, 2021, in English and related to the expression of HIF-1α in PDAC. We pooled and combined hazard ratios (HRs) and 95% confidence intervals (CIs) to show the effect of HIF-1α expression on overall survival (OS). We pooled also risk ratios (RRs) and 95% CIs to assess the correlation between HIF-1α expression and clinicopathological characteristics in PDAC. We evaluated publication bias among included studies through the Begg’s test and Egger’s test. From “Expression Plots” modules in the Gene Expression Profiling Interactive Analysis (GEPIA) database, we showed the difference of mRNA level for HIF1A between 179 pancreatic adenocarcinomas (PAADs) and 171 normal pancreatic tissues. RESULTS: This meta-analysis included 11 studies and 764 patients. High expression of HIF-1α was associated with shorter OS compared to low HIF-1α expression in PDAC (HR =1.74, 95% CI: 1.49–2.04, P<0.001). Patients with high expression of HIF-1α tended to have an increased risk of earlier lymph node metastasis (LNM) (RR =1.63, 95% CI: 1.36–1.95, P<0.001), and more advanced clinical stage (RR =1.64, 95% CI: 1.38–1.97, P<0.001) compared to those with low HIF-1α expression. Expression plots from GEPIA database showed HIF1A overexpressed in PDAC tissues compared to normal tissues (Log(2)FC =2, P<0.01). CONCLUSIONS: High HIF-1α expression associated with worse prognosis of PDACs compared to low HIF-1α expression. Since HIF-1α expression is greater in PDAC than normal pancreas, it could serve as a prognostic factor and potential therapeutic target. However, due to the complex role of HIF-1α in physiology and pathology, therapeutic intervention should be considered with caution.
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spelling pubmed-95520532022-10-12 High expression of hypoxia-inducible factor 1-alpha predicts poor prognosis in pancreatic ductal adenocarcinoma: a meta-analysis and database validation protocol Zoa, Alexis Yang, Yingjie Huang, Wenjin Yang, Jing Wang, Jiangping Wang, Haibo Dong, Minghua Tian, Yuantong Transl Cancer Res Original Article BACKGROUND: Hypoxia-inducible factor 1-alpha (HIF-1α) is overexpressed in pancreatic ductal adenocarcinomas (PDACs). However, the prognosis of high expression of HIF-1α in PDACs remains controversial because of lacking a solid support. A meta-analysis may help for a better understanding of the role of HIF-1α in the prognosis of PDACs. METHODS: By using a systematic approach, we conducted a meta-analysis from current literature. We performed an advanced search in PubMed, Embase, Cochrane Library and Web of Science databases. Recorded studies were published between September 1, 2001, and February 26, 2021, in English and related to the expression of HIF-1α in PDAC. We pooled and combined hazard ratios (HRs) and 95% confidence intervals (CIs) to show the effect of HIF-1α expression on overall survival (OS). We pooled also risk ratios (RRs) and 95% CIs to assess the correlation between HIF-1α expression and clinicopathological characteristics in PDAC. We evaluated publication bias among included studies through the Begg’s test and Egger’s test. From “Expression Plots” modules in the Gene Expression Profiling Interactive Analysis (GEPIA) database, we showed the difference of mRNA level for HIF1A between 179 pancreatic adenocarcinomas (PAADs) and 171 normal pancreatic tissues. RESULTS: This meta-analysis included 11 studies and 764 patients. High expression of HIF-1α was associated with shorter OS compared to low HIF-1α expression in PDAC (HR =1.74, 95% CI: 1.49–2.04, P<0.001). Patients with high expression of HIF-1α tended to have an increased risk of earlier lymph node metastasis (LNM) (RR =1.63, 95% CI: 1.36–1.95, P<0.001), and more advanced clinical stage (RR =1.64, 95% CI: 1.38–1.97, P<0.001) compared to those with low HIF-1α expression. Expression plots from GEPIA database showed HIF1A overexpressed in PDAC tissues compared to normal tissues (Log(2)FC =2, P<0.01). CONCLUSIONS: High HIF-1α expression associated with worse prognosis of PDACs compared to low HIF-1α expression. Since HIF-1α expression is greater in PDAC than normal pancreas, it could serve as a prognostic factor and potential therapeutic target. However, due to the complex role of HIF-1α in physiology and pathology, therapeutic intervention should be considered with caution. AME Publishing Company 2022-09 /pmc/articles/PMC9552053/ /pubmed/36237265 http://dx.doi.org/10.21037/tcr-22-787 Text en 2022 Translational Cancer Research. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Zoa, Alexis
Yang, Yingjie
Huang, Wenjin
Yang, Jing
Wang, Jiangping
Wang, Haibo
Dong, Minghua
Tian, Yuantong
High expression of hypoxia-inducible factor 1-alpha predicts poor prognosis in pancreatic ductal adenocarcinoma: a meta-analysis and database validation protocol
title High expression of hypoxia-inducible factor 1-alpha predicts poor prognosis in pancreatic ductal adenocarcinoma: a meta-analysis and database validation protocol
title_full High expression of hypoxia-inducible factor 1-alpha predicts poor prognosis in pancreatic ductal adenocarcinoma: a meta-analysis and database validation protocol
title_fullStr High expression of hypoxia-inducible factor 1-alpha predicts poor prognosis in pancreatic ductal adenocarcinoma: a meta-analysis and database validation protocol
title_full_unstemmed High expression of hypoxia-inducible factor 1-alpha predicts poor prognosis in pancreatic ductal adenocarcinoma: a meta-analysis and database validation protocol
title_short High expression of hypoxia-inducible factor 1-alpha predicts poor prognosis in pancreatic ductal adenocarcinoma: a meta-analysis and database validation protocol
title_sort high expression of hypoxia-inducible factor 1-alpha predicts poor prognosis in pancreatic ductal adenocarcinoma: a meta-analysis and database validation protocol
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9552053/
https://www.ncbi.nlm.nih.gov/pubmed/36237265
http://dx.doi.org/10.21037/tcr-22-787
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