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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ftdoajarticles:oai:doaj.org/article:0dc376d4f4df491fa39525e7c811b4c6 2023-05-15T17:42:39+02:00 Weak HIF-1alpha expression indicates poor prognosis in resectable pancreatic ductal adenocarcinoma Joni Leppänen Olli Helminen Heikki Huhta Joonas H. Kauppila Joel Isohookana Kirsi-Maria Haapasaari Seppo Parkkila Juha Saarnio Petri P. Lehenkari Tuomo J. Karttunen 2018-07-01T00:00:00Z https://doi.org/10.1186/s12957-018-1432-4 https://doaj.org/article/0dc376d4f4df491fa39525e7c811b4c6 EN eng BMC http://link.springer.com/article/10.1186/s12957-018-1432-4 https://doaj.org/toc/1477-7819 doi:10.1186/s12957-018-1432-4 1477-7819 https://doaj.org/article/0dc376d4f4df491fa39525e7c811b4c6 World Journal of Surgical Oncology, Vol 16, Iss 1, Pp 1-9 (2018) HIF-1alpha Carbonic anhydrase 9 Pancreatic ductal adenocarcinoma Surgery RD1-811 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 article 2018 ftdoajarticles https://doi.org/10.1186/s12957-018-1432-4 2022-12-31T06:28:29Z 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 Directory of Open Access Journals: DOAJ Articles World Journal of Surgical Oncology 16 1 |
institution |
Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
HIF-1alpha Carbonic anhydrase 9 Pancreatic ductal adenocarcinoma Surgery RD1-811 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
spellingShingle |
HIF-1alpha Carbonic anhydrase 9 Pancreatic ductal adenocarcinoma Surgery RD1-811 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Joni Leppänen Olli Helminen Heikki Huhta Joonas H. Kauppila Joel Isohookana Kirsi-Maria Haapasaari Seppo Parkkila Juha Saarnio Petri P. Lehenkari Tuomo J. Karttunen Weak HIF-1alpha expression indicates poor prognosis in resectable pancreatic ductal adenocarcinoma |
topic_facet |
HIF-1alpha Carbonic anhydrase 9 Pancreatic ductal adenocarcinoma Surgery RD1-811 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
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 |
Joni Leppänen Olli Helminen Heikki Huhta Joonas H. Kauppila Joel Isohookana Kirsi-Maria Haapasaari Seppo Parkkila Juha Saarnio Petri P. Lehenkari Tuomo J. Karttunen |
author_facet |
Joni Leppänen Olli Helminen Heikki Huhta Joonas H. Kauppila Joel Isohookana Kirsi-Maria Haapasaari Seppo Parkkila Juha Saarnio Petri P. Lehenkari Tuomo J. Karttunen |
author_sort |
Joni Leppänen |
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 |
BMC |
publishDate |
2018 |
url |
https://doi.org/10.1186/s12957-018-1432-4 https://doaj.org/article/0dc376d4f4df491fa39525e7c811b4c6 |
genre |
Northern Finland |
genre_facet |
Northern Finland |
op_source |
World Journal of Surgical Oncology, Vol 16, Iss 1, Pp 1-9 (2018) |
op_relation |
http://link.springer.com/article/10.1186/s12957-018-1432-4 https://doaj.org/toc/1477-7819 doi:10.1186/s12957-018-1432-4 1477-7819 https://doaj.org/article/0dc376d4f4df491fa39525e7c811b4c6 |
op_doi |
https://doi.org/10.1186/s12957-018-1432-4 |
container_title |
World Journal of Surgical Oncology |
container_volume |
16 |
container_issue |
1 |
_version_ |
1766144540466479104 |