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Opposite prognostic roles of HIF1α and HIF2α expressions in bone metastatic clear cell renal cell cancer

BACKGROUND: Prognostic markers of bone metastatic clear cell renal cell cancer (ccRCC) are poorly established. We tested prognostic value of HIF1α/HIF2α and their selected target genes in primary tumors and corresponding bone metastases. RESULTS: Expression of HIF2α was lower in mRCC both at mRNA an...

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Autores principales: Szendrői, Attila, Szász, A. Marcell, Kardos, Magdolna, Tőkés, Anna-Mária, Idan, Roni, Szűcs, Miklós, Kulka, Janina, Nyirády, Péter, Szendrői, Miklós, Szállási, Zoltán, Győrffy, Balázs, Tímár, József
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5173118/
https://www.ncbi.nlm.nih.gov/pubmed/27244898
http://dx.doi.org/10.18632/oncotarget.9669
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author Szendrői, Attila
Szász, A. Marcell
Kardos, Magdolna
Tőkés, Anna-Mária
Idan, Roni
Szűcs, Miklós
Kulka, Janina
Nyirády, Péter
Szendrői, Miklós
Szállási, Zoltán
Győrffy, Balázs
Tímár, József
author_facet Szendrői, Attila
Szász, A. Marcell
Kardos, Magdolna
Tőkés, Anna-Mária
Idan, Roni
Szűcs, Miklós
Kulka, Janina
Nyirády, Péter
Szendrői, Miklós
Szállási, Zoltán
Győrffy, Balázs
Tímár, József
author_sort Szendrői, Attila
collection PubMed
description BACKGROUND: Prognostic markers of bone metastatic clear cell renal cell cancer (ccRCC) are poorly established. We tested prognostic value of HIF1α/HIF2α and their selected target genes in primary tumors and corresponding bone metastases. RESULTS: Expression of HIF2α was lower in mRCC both at mRNA and protein levels (p/mRNA/=0.011, p/protein/=0.001) while HIF1α was similar to nmRCC. At the protein level, CAIX, GAPDH and GLUT1 were increased in mRCC. In all primary RCCs, low HIF2α and high HIF1α as well as CAIX, GAPDH and GLUT1 expressions correlated with adverse prognosis, while VEGFR2 and EPOR gene expressions were associated with favorable prognosis. Multivariate analysis confirmed high HIF2α protein expression as an independent risk factor. Prognostic validation of HIFs, LDH, EPOR and VEGFR2 in RNA-Seq data confirmed higher HIF1α gene expression in primary RCC as an adverse (p=0.07), whereas higher HIF2α and VEGFR2 expressions as favorable prognostic factors. HIF1α/HIF2α-index (HIF-index) proved to be an independent prognostic factor in both the discovery and the TCGA cohort. PATIENTS AND METHODS: Expressions of HIF1α and HIF2α as well as their 7 target genes were analysed on the mRNA and protein level in 59 non-metastatic ccRCCs (nmRCC), 40 bone metastatic primary ccRCCs (mRCC) and 55 corresponding bone metastases. Results were validated in 399 ccRCCs from the TCGA project. CONCLUSIONS: We identified HIF2α protein as an independent marker of the metastatic potential of ccRCC, however, unlike HIF1α, increased HIF2α expression is a favorable prognostic factor. The HIF-index incorporated these two markers into a strong prognostic biomarker of ccRCC.
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spelling pubmed-51731182016-12-23 Opposite prognostic roles of HIF1α and HIF2α expressions in bone metastatic clear cell renal cell cancer Szendrői, Attila Szász, A. Marcell Kardos, Magdolna Tőkés, Anna-Mária Idan, Roni Szűcs, Miklós Kulka, Janina Nyirády, Péter Szendrői, Miklós Szállási, Zoltán Győrffy, Balázs Tímár, József Oncotarget Research Paper BACKGROUND: Prognostic markers of bone metastatic clear cell renal cell cancer (ccRCC) are poorly established. We tested prognostic value of HIF1α/HIF2α and their selected target genes in primary tumors and corresponding bone metastases. RESULTS: Expression of HIF2α was lower in mRCC both at mRNA and protein levels (p/mRNA/=0.011, p/protein/=0.001) while HIF1α was similar to nmRCC. At the protein level, CAIX, GAPDH and GLUT1 were increased in mRCC. In all primary RCCs, low HIF2α and high HIF1α as well as CAIX, GAPDH and GLUT1 expressions correlated with adverse prognosis, while VEGFR2 and EPOR gene expressions were associated with favorable prognosis. Multivariate analysis confirmed high HIF2α protein expression as an independent risk factor. Prognostic validation of HIFs, LDH, EPOR and VEGFR2 in RNA-Seq data confirmed higher HIF1α gene expression in primary RCC as an adverse (p=0.07), whereas higher HIF2α and VEGFR2 expressions as favorable prognostic factors. HIF1α/HIF2α-index (HIF-index) proved to be an independent prognostic factor in both the discovery and the TCGA cohort. PATIENTS AND METHODS: Expressions of HIF1α and HIF2α as well as their 7 target genes were analysed on the mRNA and protein level in 59 non-metastatic ccRCCs (nmRCC), 40 bone metastatic primary ccRCCs (mRCC) and 55 corresponding bone metastases. Results were validated in 399 ccRCCs from the TCGA project. CONCLUSIONS: We identified HIF2α protein as an independent marker of the metastatic potential of ccRCC, however, unlike HIF1α, increased HIF2α expression is a favorable prognostic factor. The HIF-index incorporated these two markers into a strong prognostic biomarker of ccRCC. Impact Journals LLC 2016-05-27 /pmc/articles/PMC5173118/ /pubmed/27244898 http://dx.doi.org/10.18632/oncotarget.9669 Text en Copyright: © 2016 Szendrői et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Szendrői, Attila
Szász, A. Marcell
Kardos, Magdolna
Tőkés, Anna-Mária
Idan, Roni
Szűcs, Miklós
Kulka, Janina
Nyirády, Péter
Szendrői, Miklós
Szállási, Zoltán
Győrffy, Balázs
Tímár, József
Opposite prognostic roles of HIF1α and HIF2α expressions in bone metastatic clear cell renal cell cancer
title Opposite prognostic roles of HIF1α and HIF2α expressions in bone metastatic clear cell renal cell cancer
title_full Opposite prognostic roles of HIF1α and HIF2α expressions in bone metastatic clear cell renal cell cancer
title_fullStr Opposite prognostic roles of HIF1α and HIF2α expressions in bone metastatic clear cell renal cell cancer
title_full_unstemmed Opposite prognostic roles of HIF1α and HIF2α expressions in bone metastatic clear cell renal cell cancer
title_short Opposite prognostic roles of HIF1α and HIF2α expressions in bone metastatic clear cell renal cell cancer
title_sort opposite prognostic roles of hif1α and hif2α expressions in bone metastatic clear cell renal cell cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5173118/
https://www.ncbi.nlm.nih.gov/pubmed/27244898
http://dx.doi.org/10.18632/oncotarget.9669
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