Prognostic role of hypoxia-inducible factor-1 alpha expression in osteosarcoma: a meta-analysis

Ren, Haiyong; Zhang, Yinhua; Li, Hengyuan; Xie, Tao; Sun, Lingling; Zhu, Ting; Wang, Shengdong; Ye, Zhaoming

doi:10.2147/ott.s95490

Cited by 23 publications

(17 citation statements)

References 47 publications

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“…HIF-1α is highly expressed in hypoxic conditions and is recognized as a predictor of tumor diagnosis and recrudescence, monitor of invasion and metastasis, and marker of malignant grades in OS [ 38 ]. However, it has also been well demonstrated that HIF-1α is expressed in normal and malignant bone cell lines during normoxia, and is especially high in OS cells [ 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

Tetrahydrocurcumin induces mesenchymal-epithelial transition and suppresses angiogenesis by targeting HIF-1α and autophagy in human osteosarcoma

et al. 2017

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Human osteosarcoma is considered a malignant tumor with poor prognosis that readily metastasizes. Tetrahydrocurcumin (THC) has been reported to have antitumor activity in numerous tumors. In addition, hypoxia-inducible factor-1α (HIF-1α) has been demonstrated to be associated with tumor metastasis by regulating epithelial-mesenchymal transition (EMT). However, the role of THC in osteosarcoma remains uncertain. Therefore, this study aimed to elucidate the potential mechanisms. We found that THC significantly reduced the growth of osteosarcoma cells and suppressed migration and invasion, as tested in a nude mouse lung metastasis model. Additionally, the mesenchymal-epithelial transition (MET) process was facilitated by THC. Mechanistically, our study showed that HIF-1α had a pivotal role in the antimetastatic effect of THC. Importantly, HIF-1α expression was downregulated by THC by inhibiting Akt/mTOR and p38 MAPK pathways. Moreover, THC exhibited a remarkable inhibitory effect on HIF-1α expression and angiogenesis under hypoxic conditions. Furthermore, THC activated autophagy and induced MET and suppressed angiogenesis in a HIF-1α-related manner. Taken together, our findings suggest that THC suppresses metastasis and invasion and this may be associated with HIF-1α and autophagy, which would potentially provide therapeutic strategies for human osteosarcoma.

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Section: Discussionmentioning

confidence: 99%

Tetrahydrocurcumin induces mesenchymal-epithelial transition and suppresses angiogenesis by targeting HIF-1α and autophagy in human osteosarcoma

et al. 2017

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“…However, in the past 20 years, there were no further improvements in osteosarcoma survival. To explain this lack of progress, many studies were performed to investigate factors effecting the progression and metastasis of osteosarcoma, such as levels of C-reactive protein and expression of hypoxia-inducible factor-1 alpha [ 25 , 26 ]. There are several studies which have assessed the association between pathological fracture and prognosis in patients with osteosarcoma; however, the results were inconclusive because of the limited sample of single-study.…”

Section: Discussionmentioning

confidence: 99%

The effect of pathological fractures on the prognosis of patients with osteosarcoma: a meta-analysis of 14 studies

Zhou

Lü

et al. 2017

Oncotarget

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Osteosarcoma is a leading cause of malignant tumor related death. We conducted a meta-analysis to evaluate the association between pathological fractures and prognosis in patients with osteosarcoma. We searched PubMed, Web of Science, and Embase for studies published until May 15, 2017. Crude and adjusted relative risk (RR) with 95% confidence intervals were used to compare data between the case and control groups. Fourteen studies and 3910 patients were included in the final meta-analysis. No statistically significant difference was detected between the pathological fracture and non-pathological fracture groups in local recurrences analysis (RR = 1.102, 95% CI: 0.813–1.495, P = 0.531); however, a statistically significant difference was found between group in distant metastasis (RR = 1.424, 95% CI: 1.089–1.862, P = 0.01). For survival rates, the following RRs were calculated: 3-year overall survival (OS) (RR = 0.736, 95% CI: 0.593–0.912, P = 0.005); 5-year OS (RR = 0.889, 95% CI: 0.791–0.999, P = 0.049); 3-year event-free survival (EFS) (RR = 0.812, 95% CI: 0.682–0.966, P = 0.018); and 5-year EFS (RR = 0.876, 95% CI: 0.785–0.978, P = 0.019). The pooled estimate of RR was 0.673 (95% CI: 0.364–1.244, P = 0.206) for local recurrence in the amputation and limb salvage groups. In conclusion, our analysis indicated that there were no differences in local recurrence and local recurrence after limb salvage between patients with or without a fracture. Additionally, the patients with pathological fracture had a higher risk of distant metastasis and lower 3-year OS, 5-year OS, 3-year EFS, and 5-year EFS. Considering the limitations of this study, we believe that future large-scale studies should be performed to confirm our conclusions.

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“…The downregulation of HIF-1α suppresses OS cell growth by inducing apoptosis [59], and the HIF-1α/CXCR4 pathways contribute to metastasis in human OS cells [60]. A recent meta-analysis has suggested that overexpression of HIF-1α is a predictive factor for poor outcomes in OS and could serve as a promising prognostic biomarker to predict the outcome of OS patients [61,62].…”

Section: Hypoxiamentioning

confidence: 99%

Microenvironment Signals and Mechanisms in the Regulation of Osteosarcoma

Mai¹,

Zhang²,

Xie³

et al. 2017

Osteosarcoma - Biology, Behavior and Mechanisms

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Osteosarcoma (OS) is the most common malignant primary bone tumor in children and adolescents and features rapid development, strong metastatic ability, and poor prognosis. It has been well established that diverse genetic aberrations and metabolic alterations confer the tumorigenesis and development of OS. The intricate metabolism and vascularization that contributes to the nutrient and structural support for tumor progression should be thoroughly clariied to help us gain novel insights into OS and its clinical diagnoses and treatments. With regard to the complex bone extracellular matrix (ECM) and local cell populations, we intend to illustrate the interrelationship between various microenvironmental signals and the diferent stages of OS evolution. Solid evidence has noted two crucial factors of the OS microenvironment in the acquisition of stem cell phenotypes -transforming growth factor-β1 (TGF-β1) signaling and hypoxia. Diferent cell subtypes in the local environment might also serve as unique contributors that interact with each other and communicate with distant cells, thus participating in local invasion and metastasis. Proper models have been established and improved to reveal the evolutionary footsteps of how normal cells transform into a neoplastic state and progress toward malignancy.

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Prognostic role of hypoxia-inducible factor-1 alpha expression in osteosarcoma: a meta-analysis

Cited by 23 publications

References 47 publications

Tetrahydrocurcumin induces mesenchymal-epithelial transition and suppresses angiogenesis by targeting HIF-1α and autophagy in human osteosarcoma

Tetrahydrocurcumin induces mesenchymal-epithelial transition and suppresses angiogenesis by targeting HIF-1α and autophagy in human osteosarcoma

The effect of pathological fractures on the prognosis of patients with osteosarcoma: a meta-analysis of 14 studies

Microenvironment Signals and Mechanisms in the Regulation of Osteosarcoma

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