Prognosis value of HIF-1α expression in patients with non-small cell lung cancer

Wang, Qian; Hu, Dan-feng; Yan, Rui; Jiang, Anbang; Liu, Zili; Huang, Lingxia

doi:10.1016/j.gene.2014.03.025

Cited by 44 publications

(35 citation statements)

References 29 publications

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“…This result is in agreement with findings from previous studies that showed that lung cancer patients with high HIF-2α levels had a poor prognosis after treatment, and that HIF-2α was a predictive factor for prognosis (Wu et al, 2011;Wang et al, 2014b). Although our study focused on the relationship between pre-radiation HIF-2α levels and prognosis while previous studies focused on the relationship between post-radiation HIF-2α levels and prognosis, the results from both methods revealed a negative correlation between HIF-2α levels and prognosis in lung cancer.…”

Section: Discussionsupporting

confidence: 93%

“…For example, HIF-1α inhibits apoptosis and promotes the proliferation of lung cancer cells (Volm and Koomagi, 2000;Fan et al, 2002), regulates the tolerance to palladium drugs (Song et al, 2006), promotes angiogenesis in lung cancer (Jackson et al, 2010), promotes the proliferation of cancer cells (Wang et al, 2013), and promotes the migration of lung cancer cells (Li et al, 2009b). HIF-1α expression is significantly upregulated after surgery or radiotherapy (Zhang et al, 2009); therefore, HIF-1α may serve as a biomarker to evaluate prognosis (Luan et al, 2013;Wang et al, 2014b), or serve as a target for treatment (Jacoby et al, 2010;Zhang et al, 2012). However, the role of HIF-2α in lung cancer has rarely been reported on.…”

Section: Introductionmentioning

confidence: 99%

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High expression of HIF-2α and its anti-radiotherapy effect in lung cancer stem cells

Sun¹,

He²,

Yi³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Hypoxia-inducible factor-2 alpha (HIF-2α) has been shown to regulate cell stemness, although the expression and effects of HIF-2α in lung cancer stem cells remained unclear. This study investigated HIF-2α expression in lung cancer stem cells, as well as the relationship between HIF-2α expression and radioresistance in lung cancer cells. Stem-like cells (CD133 + ) in the non-small-cell lung cancer cell line A549 were enriched by serum-free culture conditions, and CD133 + cells were sorted via fluorescence-activated cell sorting. A549 cells were treated with middle-infrared radiation, and the level of HIF-2α expression was determined by a quantitative polymerase chain reaction assay and western blot analysis. The level of HIF-2α expression in tissue sections from 50 cases of clinically confirmed non-small-cell lung cancer was determined via immunohistochemical analysis, and its correlation with prognosis after radiotherapy was analyzed. HIF-2α levels in CD133 + cells were significantly higher than those in CD133 -cells (P = 0.032). However, after radiation treatment, these levels were significantly upregulated in both CD133+ and CD133 -cells (P = 0.031 and P = 0.023, respectively). After irradiation, the proportions of apoptotic, dead, and autophagic CD133 + A549 cells were 18111 HIF-2α and radioresistance in lung cancer stem cells ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 18110-18120 (2015) considerably lower than those of CD133 -A549 cells (P < 0.05). Furthermore, the recovery of carcinoembryonic antigen to pre-radiation levels was more rapid in lung cancer patients with high levels of HIF-2α expression, and these patients had shorter survival times (P = 0.018). HIF-2α is highly expressed in lung cancer stem cells, which may lead to radioresistance. In conclusion, HIF-2α is a potential prognostic marker for lung cancer.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

High expression of HIF-2α and its anti-radiotherapy effect in lung cancer stem cells

Sun¹,

He²,

Yi³

et al. 2015

Genet. Mol. Res.

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“…Under hypoxia condition, HIF-1α becomes stabilized and forms an active transcriptional complex with HIF-1β and up-regulates expression of down-stream genes, which are required for cancer cells to survive and invade [20]. HIF-1α is often over-expressed in malignant cells and links to poor prognosis in lung cancer [21]. Our results showed that the protein level of HIF-1α was up-regulated markedly when cells were in hypoxic condition.…”

Section: Discussionmentioning

confidence: 83%

Sevoflurane suppresses hypoxia-induced growth and metastasis of lung cancer cells via inhibiting hypoxia-inducible factor-1α

et al. 2015

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“…7,14 Increase of HIF-1α and hypoxia-related proteins are associated with poor outcome in lung cancer patients. 15 However, how cancer cells adapt to hypoxia and communicate with TME during tumour development remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Hypoxic lung cancer-secreted exosomal miR-23a increased angiogenesis and vascular permeability by targeting prolyl hydroxylase and tight junction protein ZO-1

et al. 2017

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Hypoxia plays a critical role during the evolution of malignant cells and tumour microenvironment (TME).Tumour-derived exosomes contain informative microRNAs involved in the interaction of cancer and stromal cells, thus contributing to tissue remodelling of tumour microenvironment. This study aims to clarify how hypoxia affects tumour angiogenesis through exosomes shed from lung cancer cells. Lung cancer cells produce more exosomes under hypoxic conditions than do parental cells under normoxic conditions. miR-23a was significantly upregulated in exosomes from lung cancer under hypoxic conditions. Exosomal miR-23a directly suppressed its target prolyl hydroxylase 1 and 2 (PHD1 and 2), leading to the accumulation of hypoxia-inducible factor-1 α (HIF-1 α) in endothelial cells. Consequently, hypoxic lung cancer cells enhanced angiogenesis by exosomes derived from hypoxic cancer under both normoxic and hypoxic conditions. In addition, exosomal miR-23a also inhibits tight junction protein ZO-1, thereby increasing vascular permeability and cancer transendothelial migration. Inhibition of miR-23a by inhibitor administration decreased angiogenesis and tumour growth in a mouse model. Furthermore, elevated levels of circulating miR-23a are found in the sera of lung cancer patients, and miR-23a levels are positively correlated with proangiogenic activities. Taken together, our study reveals the clinical relevance and prognostic value of cancer-derived exosomal miR-23a under hypoxic conditions, and investigates a unique intercellular communication, mediated by cancer-derived exosomes, which modulates tumour vasculature.

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Prognosis value of HIF-1α expression in patients with non-small cell lung cancer

Cited by 44 publications

References 29 publications

High expression of HIF-2α and its anti-radiotherapy effect in lung cancer stem cells

High expression of HIF-2α and its anti-radiotherapy effect in lung cancer stem cells

Sevoflurane suppresses hypoxia-induced growth and metastasis of lung cancer cells via inhibiting hypoxia-inducible factor-1α

Hypoxic lung cancer-secreted exosomal miR-23a increased angiogenesis and vascular permeability by targeting prolyl hydroxylase and tight junction protein ZO-1

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