Combined over-expression of the hypoxia-inducible factor 2α gene and its long non-coding RNA predicts unfavorable prognosis of patients with osteosarcoma.
BACKGROUND
LncRNA hypoxia-inducible factor-2α (HIF-2α) promoter upstream transcript (HIF2PUT) functions as a novel regulatory factor of osteosarcoma stem cells partly by controlling HIF-2α expression. The aim of this study was to investigate the clinical significance of HIF-2α and HIF2PUT in human osteosarcoma.


METHODS
Quantitative real-time PCR was performed to detect the expression levels of HIF-2α mRNA and HIF2PUT in 82 surgical specimens of primary osteosarcoma and matched non-cancerous bone tissues. Then, the associations of HIF-2α and/or HIF2PUT expression with various clinicopathological features of osteosarcoma patients were statistically analyzed. Moreover, their prognostic value was further evaluated.


RESULTS
Compared with non-cancerous bone tissues, HIF-2α mRNA and HIF2PUT expression were both significantly upregulated in osteosarcoma tissues (all P<0.001). Interestingly, the expression levels of HIF-2α mRNA in osteosarcoma tissues were positively correlated with those of HIF2PUT (r=0.28, P=0.009). Additionally, osteosarcoma patients with HIF-2α mRNA and/or HIF2PUT over-expression more frequently had large tumor size (all P<0.05), advanced clinical stage (all P<0.01) and positive distant metastasis (all P<0.01). Moreover, osteosarcoma patients with HIF-2α mRNA and/or HIF2PUT over-expression had a significantly shorter overall and disease-free survival (all P<0.05). Furthermore, Cox multivariate analysis identified that HIF-2α mRNA and/or HIF2PUT expression, clinical stage and distant metastasis were all independent and significant prognostic factors for both overall and disease-free survival (all P<0.05).


CONCLUSIONS
HIF-2α and HIF2PUT upregulation may be a common feature in human osteosarcomas with aggressive potency. The over-expression of the two molecules, alone or combined, may predict poor prognosis in osteosarcoma patients.
Department of Orthopedics, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China; Department of Anesthesia, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Wei
W
Li
Department of Orthopedics, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. Electronic address: xijing_h@vip.tom.com.
Xijing
X
He
Department of Anesthesia, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Rongliang
R
Xue
Department of Anesthesia, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Ying
Y
Zhang
Department of Anesthesia, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Xiaoqin
X
Zhang
Department of Anesthesia, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Jianrui
J
Lu
Department of Anesthesia, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Zhenni
Z
Zhang
Department of Anesthesia, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Li
L
Xue
D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D015996:Survival Rate; D015854:Up-Regulation; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D062085:RNA, Long Noncoding; D000099162:Endothelial PAS Domain-Containing Protein 1
Clinicopathologic features; Hypoxia-inducible factor 2α; Hypoxia-inducible factor-2α; Long non-coding RNA; Osteosarcoma; Prognosis; Promoter upstream transcript