TY - JOUR
T1 - Opposite prognostic roles of HIF1β and HIF2β expressions in bone metastatic clear cell renal cell cancer
AU - Szendroi, Attila
AU - Szász, A. Marcell
AU - Kardos, Magdolna
AU - Tőkés, Anna-Mária
AU - Idan, Roni
AU - Szűcs, Miklós
AU - Kulka, Janina
AU - Nyirady, Péter
AU - Szendrői, Miklós
AU - Szallasi, Zoltan Imre
AU - Győrffy, Balázs
AU - Tímár, József
N1 - All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PY - 2016
Y1 - 2016
N2 - BACKGROUND: Prognostic markers of bone metastatic clear cell renal cell cancer (ccRCC) are poorly established. We tested prognostic value of HIF1β/HIF2β and their selected target genes in primary tumors and corresponding bone metastases. RESULTS: Expression of HIF2β was lower in mRCC both at mRNA and protein levels (p/mRNA/ = 0.011, p/protein/ = 0.001) while HIF1β was similar to nmRCC. At the protein level, CAIX, GAPDH and GLUT1 were increased in mRCC. In all primary RCCs, low HIF2β and high HIF1β 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 HIF1β gene expression in primary RCC as an adverse (p = 0.07), whereas higher HIF2β and VEGFR2 expressions as favorable prognostic factors. HIF1β/HIF2β-index (HIF-index) proved to be an independent prognostic factor in both the discovery and the TCGA cohort.PATIENTS AND METHODS: Expressions of HIF1β and HIF2β 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 HIF2β protein as an independent marker of the metastatic potential of ccRCC, however, unlike HIF1β, increased HIF2β expression is a favorable prognostic factor. The HIF-index incorporated these two markers into a strong prognostic biomarker of ccRCC.
AB - BACKGROUND: Prognostic markers of bone metastatic clear cell renal cell cancer (ccRCC) are poorly established. We tested prognostic value of HIF1β/HIF2β and their selected target genes in primary tumors and corresponding bone metastases. RESULTS: Expression of HIF2β was lower in mRCC both at mRNA and protein levels (p/mRNA/ = 0.011, p/protein/ = 0.001) while HIF1β was similar to nmRCC. At the protein level, CAIX, GAPDH and GLUT1 were increased in mRCC. In all primary RCCs, low HIF2β and high HIF1β 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 HIF1β gene expression in primary RCC as an adverse (p = 0.07), whereas higher HIF2β and VEGFR2 expressions as favorable prognostic factors. HIF1β/HIF2β-index (HIF-index) proved to be an independent prognostic factor in both the discovery and the TCGA cohort.PATIENTS AND METHODS: Expressions of HIF1β and HIF2β 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 HIF2β protein as an independent marker of the metastatic potential of ccRCC, however, unlike HIF1β, increased HIF2β expression is a favorable prognostic factor. The HIF-index incorporated these two markers into a strong prognostic biomarker of ccRCC.
U2 - 10.18632/oncotarget.9669
DO - 10.18632/oncotarget.9669
M3 - Journal article
C2 - 27244898
SN - 1949-2553
VL - 7
SP - 42086
EP - 42098
JO - OncoTarget
JF - OncoTarget
IS - 27
ER -
