Weak HIF-1alpha expression indicates poor prognosis in resectable pancreatic ductal adenocarcinoma
Abstract Background HIF-1alpha and CAIX proteins are commonly expressed under hypoxic conditions, but other regulatory factors have been described as well. Pancreatic ductal adenocarcinoma (PDAC) is characterized by hypoxia and strong stromal reaction and has a dismal prognosis with the currently av...
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ftdatacite:10.6084/m9.figshare.c.4154051 2023-05-15T17:42:38+02:00 Weak HIF-1alpha expression indicates poor prognosis in resectable pancreatic ductal adenocarcinoma Leppänen, Joni Helminen, Olli Huhta, Heikki Kauppila, Joonas Isohookana, Joel Kirsi-Maria Haapasaari Parkkila, Seppo Saarnio, Juha Lehenkari, Petri Karttunen, Tuomo 2018 https://dx.doi.org/10.6084/m9.figshare.c.4154051 https://figshare.com/collections/Weak_HIF-1alpha_expression_indicates_poor_prognosis_in_resectable_pancreatic_ductal_adenocarcinoma/4154051 unknown Figshare https://dx.doi.org/10.1186/s12957-018-1432-4 CC BY 4.0 https://creativecommons.org/licenses/by/4.0 CC-BY Biochemistry Medicine Cell Biology Genetics FOS Biological sciences Molecular Biology Biotechnology Immunology FOS Clinical medicine Cancer Computational Biology Collection article 2018 ftdatacite https://doi.org/10.6084/m9.figshare.c.4154051 https://doi.org/10.1186/s12957-018-1432-4 2021-11-05T12:55:41Z Abstract Background HIF-1alpha and CAIX proteins are commonly expressed under hypoxic conditions, but other regulatory factors have been described as well. Pancreatic ductal adenocarcinoma (PDAC) is characterized by hypoxia and strong stromal reaction and has a dismal prognosis with the currently available treatment modalities. Methods We investigated the expression and prognostic role of HIF-1alpha and CAIX in PDAC series from Northern Finland (n = 69) using immunohistochemistry. Results In our PDAC cases, 95 and 85% showed HIF-1alpha and CAIX expression, respectively. Low HIF-1alpha expression correlated with poor prognosis, and multivariate analysis identified weak HIF-1alpha intensity as an independent prognostic factor for PDAC-specific deaths (HR 2.176, 95% CI 1.216–3.893; p = 0.009). There was no correlation between HIF-1alpha and CAIX expression levels, and the latter did not relate with survival. Conclusions Our findings are in contrast with previous research by finding an association between low HIF-1alpha and poor prognosis. The biological mechanisms remain speculative, but such an unexpected relation with prognosis and absence of correlation between HIF-1alpha and CAIX suggests that the prognostic association of HIF-1alpha may not directly be linked with hypoxia. Accordingly, the role of HIF-1alpha might be more complex than previously thought and the use of this marker as a hypoxia-related prognostic factor should be addressed with caution. Article in Journal/Newspaper Northern Finland DataCite Metadata Store (German National Library of Science and Technology) |
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DataCite Metadata Store (German National Library of Science and Technology) |
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language |
unknown |
topic |
Biochemistry Medicine Cell Biology Genetics FOS Biological sciences Molecular Biology Biotechnology Immunology FOS Clinical medicine Cancer Computational Biology |
spellingShingle |
Biochemistry Medicine Cell Biology Genetics FOS Biological sciences Molecular Biology Biotechnology Immunology FOS Clinical medicine Cancer Computational Biology Leppänen, Joni Helminen, Olli Huhta, Heikki Kauppila, Joonas Isohookana, Joel Kirsi-Maria Haapasaari Parkkila, Seppo Saarnio, Juha Lehenkari, Petri Karttunen, Tuomo Weak HIF-1alpha expression indicates poor prognosis in resectable pancreatic ductal adenocarcinoma |
topic_facet |
Biochemistry Medicine Cell Biology Genetics FOS Biological sciences Molecular Biology Biotechnology Immunology FOS Clinical medicine Cancer Computational Biology |
description |
Abstract Background HIF-1alpha and CAIX proteins are commonly expressed under hypoxic conditions, but other regulatory factors have been described as well. Pancreatic ductal adenocarcinoma (PDAC) is characterized by hypoxia and strong stromal reaction and has a dismal prognosis with the currently available treatment modalities. Methods We investigated the expression and prognostic role of HIF-1alpha and CAIX in PDAC series from Northern Finland (n = 69) using immunohistochemistry. Results In our PDAC cases, 95 and 85% showed HIF-1alpha and CAIX expression, respectively. Low HIF-1alpha expression correlated with poor prognosis, and multivariate analysis identified weak HIF-1alpha intensity as an independent prognostic factor for PDAC-specific deaths (HR 2.176, 95% CI 1.216–3.893; p = 0.009). There was no correlation between HIF-1alpha and CAIX expression levels, and the latter did not relate with survival. Conclusions Our findings are in contrast with previous research by finding an association between low HIF-1alpha and poor prognosis. The biological mechanisms remain speculative, but such an unexpected relation with prognosis and absence of correlation between HIF-1alpha and CAIX suggests that the prognostic association of HIF-1alpha may not directly be linked with hypoxia. Accordingly, the role of HIF-1alpha might be more complex than previously thought and the use of this marker as a hypoxia-related prognostic factor should be addressed with caution. |
format |
Article in Journal/Newspaper |
author |
Leppänen, Joni Helminen, Olli Huhta, Heikki Kauppila, Joonas Isohookana, Joel Kirsi-Maria Haapasaari Parkkila, Seppo Saarnio, Juha Lehenkari, Petri Karttunen, Tuomo |
author_facet |
Leppänen, Joni Helminen, Olli Huhta, Heikki Kauppila, Joonas Isohookana, Joel Kirsi-Maria Haapasaari Parkkila, Seppo Saarnio, Juha Lehenkari, Petri Karttunen, Tuomo |
author_sort |
Leppänen, Joni |
title |
Weak HIF-1alpha expression indicates poor prognosis in resectable pancreatic ductal adenocarcinoma |
title_short |
Weak HIF-1alpha expression indicates poor prognosis in resectable pancreatic ductal adenocarcinoma |
title_full |
Weak HIF-1alpha expression indicates poor prognosis in resectable pancreatic ductal adenocarcinoma |
title_fullStr |
Weak HIF-1alpha expression indicates poor prognosis in resectable pancreatic ductal adenocarcinoma |
title_full_unstemmed |
Weak HIF-1alpha expression indicates poor prognosis in resectable pancreatic ductal adenocarcinoma |
title_sort |
weak hif-1alpha expression indicates poor prognosis in resectable pancreatic ductal adenocarcinoma |
publisher |
Figshare |
publishDate |
2018 |
url |
https://dx.doi.org/10.6084/m9.figshare.c.4154051 https://figshare.com/collections/Weak_HIF-1alpha_expression_indicates_poor_prognosis_in_resectable_pancreatic_ductal_adenocarcinoma/4154051 |
genre |
Northern Finland |
genre_facet |
Northern Finland |
op_relation |
https://dx.doi.org/10.1186/s12957-018-1432-4 |
op_rights |
CC BY 4.0 https://creativecommons.org/licenses/by/4.0 |
op_rightsnorm |
CC-BY |
op_doi |
https://doi.org/10.6084/m9.figshare.c.4154051 https://doi.org/10.1186/s12957-018-1432-4 |
_version_ |
1766144533976842240 |