Dataset Information

Prognostic Role of Hypoxia-Inducible Factor-2? Tumor Cell Expression in Cancer Patients: A Meta-Analysis.

ABSTRACT: Hypoxia-inducible factor-2? (HIF-2?) plays an important role in tumor progression and metastasis. A number of studies have evaluated the correlation between HIF-2? overexpression and clinical outcome in cancer patients but yielded inconsistent results. To comprehensively and quantitatively summarize the evidence on the capability of HIF-2? to predict the prognosis of cancer patients with solid tumors, a meta-analysis was carried out. Renal cell carcinoma (CC-RCC) was separately analyzed due to an alternative mechanism of regulation. Systematic literature searches were performed in PubMed and Embase databases for relevant original articles until February 2018. Forty-nine studies with 6,052 patients were included in this study. The pooled hazard ratios (HRs) with corresponding confidence intervals were calculated to assess the prognostic value of HIF-2? protein expression in tumor cells. The meta-analysis revealed strong significant negative associations between HIF-2? expression and five endpoints: overall survival [HR?=?1.69, 95% confidence interval (95% CI) 1.39-2.06], disease-free survival (HR?=?1.87, 95% CI 1.2-2.92), disease-specific survival (HR?=?1.57, 95% CI 1.06-2.34), metastasis-free survival (HR?=?2.67, 95% CI 1.32-5.38), and progression-free survival (HR?=?2.18, 95% CI 1.25-3.78). Subgroup analyses revealed similar associations in the majority of tumor sites. Overall, these data demonstrate a negative prognostic role of HIF-2? in patients suffering from different types of solid tumors.

SUBMITTER: Moreno Roig E

PROVIDER: S-EPMC6004384 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Prognostic Role of Hypoxia-Inducible Factor-2α Tumor Cell Expression in Cancer Patients: A Meta-Analysis.

Moreno Roig Eloy E Yaromina Ala A Houben Ruud R Groot Arjan J AJ Dubois Ludwig L Vooijs Marc M

Frontiers in oncology 20180611

Hypoxia-inducible factor-2α (HIF-2α) plays an important role in tumor progression and metastasis. A number of studies have evaluated the correlation between HIF-2α overexpression and clinical outcome in cancer patients but yielded inconsistent results. To comprehensively and quantitatively summarize the evidence on the capability of HIF-2α to predict the prognosis of cancer patients with solid tumors, a meta-analysis was carried out. Renal cell carcinoma (CC-RCC) was separately analyzed due to a ...[more]

PMID: 29942795

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Project description:BackgroundRecently, many studies have shown the role of hypoxia-inducible factor-1α (HIF-1α) expression in the outcome of bone tumor. However, the results remain inconclusive. It is necessary to carry out a meta-analysis of all the current available data to clarify the relationship between HIF-1α and survival or clinicopathological features of bone tumor.MethodsPubMed, Cochrane Library, Web of Science, China National Knowledge Internet, and Wanfang databases were used to search the relationship between HIF-1α and bone tumor. Articles investigating clinicopathological and prognostic value of HIF-1α in bone tumor patients were enrolled in this meta-analysis. Overlapping articles, duplicate data, reviews, case reports, and letters without original data were excluded. The pooled risk ratios (RRs) and hazard ratios (HRs) were used to evaluate the clinicopathological and prognostic value of HIF-1α on bone tumor patients, respectively.ResultsA total of 28 studies including 1443 patients were included in this meta-analysis, which were involved in three different types of bone tumor including 3 chondrosarcomas, 2 giant cell tumors of bone, and 23 osteosarcomas. Our results showed that high expression levels of HIF-1α were associated with poorer OS (overall survival) (HR = 2.61, 95% CI 2.11-3.23, P < 0.001) and shorter DFS (disease-free survival) (HR = 2.02, 95% CI 1.41-2.89, P < 0.001) in bone tumor. In addition, this study also analyzed the role of HIF-1α expression in clinicopathological features, which were closely related with the severity of bone tumor, including differentiation, clinical stage, metastasis, and microvessel density. Our results indicated that HIF-1α overexpression was significantly associated with differentiation (RR = 1.56, 95% CI 1.00-2.43, P = 0.049), clinical stage (RR = 1.75, 95% CI 1.25-2.45, P = 0.001), metastasis (RR = 1.78, 95% CI 1.58-2.00, P < 0.001), and microvessel density (SMD = 2.34, 95% CI 1.35-3.34, P < 0.001) of bone tumor.ConclusionsHIF-1α overexpression indicated an unfavorable factor for OS and DFS in bone tumor, suggesting that HIF-1α may serve as a potential prognostic marker for bone tumor.

Project description:IntroductionOverexpression of the oxygen-responsive transcription factor hypoxia-inducible factor 1α (HIF-1α) correlates with poor prognosis in breast cancer patients. The mouse mammary tumor virus polyoma virus middle T (MMTV-PyMT) mouse is a widely utilized preclinical mouse model that resembles human luminal breast cancer and is highly metastatic. Prior studies in which the PyMT model was used demonstrated that HIF-1α is essential to promoting carcinoma onset and lung metastasis, although no differences in primary tumor end point size were observed. Using a refined model system, we investigated whether HIF-1α is directly implicated in the regulation of tumor-initiating cells (TICs) in breast cancer.MethodsMammary tumor epithelial cells were created from MMTV-PyMT mice harboring conditional alleles of Hif1a, followed by transduction ex vivo with either adenovirus β-galactosidase or adenovirus Cre to generate wild-type (WT) and HIF-1α-null (KO) cells, respectively. The impact of HIF-1α deletion on tumor-initiating potential was investigated using tumorsphere assays, limiting dilution transplantation and gene expression analysis.ResultsEfficient deletion of HIF-1α reduced primary tumor growth and suppressed lung metastases, prolonging survival. Loss of HIF-1α led to reduced expression of markers of the basal lineage (K5/K14) in cells and tumors and of multiple genes involved in the epithelial-to-mesenchymal transition. HIF-1α also enhanced tumorsphere formation at normoxia and hypoxia. Decreased expression of several genes in the Notch pathway as well as Vegf and Prominin-1 (CD133)was observed in response to Hif1a deletion. Immunohistochemistry confirmed that CD133 expression was reduced in KO cells and in tumorspheres. Tumorsphere formation was enhanced in CD133hi versus CD133neg cells sorted from PyMT tumors. Limiting dilution transplantation of WT and KO tumor cells into immunocompetent recipients revealed > 30-fold enrichment of TICs in WT cells.ConclusionThese results demonstrate that HIF-1α plays a key role in promoting primary mammary tumor growth and metastasis, in part through regulation of TICs. HIF-1α regulates expression of several members of the Notch pathway, CD133 and markers of the basal lineage in mammary tumors. Our results suggest that CD133, which has not been profiled extensively in breast cancer, may be a useful marker of TICs in the PyMT mouse model. These data reveal for the first time that HIF-1α directly regulates breast TIC activity in vivo.

Dataset Information

Prognostic Role of Hypoxia-Inducible Factor-2? Tumor Cell Expression in Cancer Patients: A Meta-Analysis.

Publications

Prognostic Role of Hypoxia-Inducible Factor-2α Tumor Cell Expression in Cancer Patients: A Meta-Analysis.

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